Scholars@Duke
Vadim Y Arshavsky

Vadim Y Arshavsky

Helena Rubinstein Foundation Distinguished Professor of Ophthalmology
Ophthalmology, Vitreoretinal Diseases & Surgery
vadim.arshavsky@duke.edu
Box 3802 Med Ctr, Durham, NC 27710
Duke Eye Center, 2351 Erwin Rd. Box 3802, 5012 Aeri, Durham, NC 27710

Selected Publications

Inpp5e is a Critical Regulator of Protein Transport to Photoreceptor Outer Segments.

Journal Article bioRxiv · August 28, 2024 In humans, inositol polyphosphate-5-phosphatase e (INPP5E) mutations cause retinal degeneration as part of Joubert and MORM syndromes and can also cause non-syndromic blindness. In mice, mutations cause a spectrum of brain, kidney, and other anomalies and ... Full text Link to item Cite

Acyl-CoA synthetase 6 controls rod photoreceptor function and survival by shaping the phospholipid composition of retinal membranes.

Journal Article Commun Biol · August 21, 2024 The retina is light-sensitive neuronal tissue in the back of the eye. The phospholipid composition of the retina is unique and highly enriched in polyunsaturated fatty acids, including docosahexaenoic fatty acid (DHA). While it is generally accepted that a ... Full text Link to item Cite

Contribution of intraflagellar transport to compartmentalization and maintenance of the photoreceptor cell.

Journal Article Proc Natl Acad Sci U S A · August 20, 2024 The first steps of vision take place in the ciliary outer segment compartment of photoreceptor cells. The protein composition of outer segments is uniquely suited to perform this function. The most abundant among these proteins is the visual pigment, rhodo ... Full text Link to item Cite

Vision: A specialized pathway for pigment regeneration in cones.

Journal Article Curr Biol · August 5, 2024 Vision relies on two types of photoreceptor cells, rods and cones. Rods outnumber cones in the retinas of humans and most other vertebrate species, yet the contribution of cones to our vision is far more impactful than rods. A new study reveals an elegant ... Full text Link to item Cite

The Structural and Functional Integrity of Rod Photoreceptor Ribbon Synapses Depends on Redundant Actions of Dynamins 1 and 3.

Journal Article J Neurosci · June 19, 2024 Vertebrate vision begins with light absorption by rod and cone photoreceptors, which transmit signals from their synaptic terminals to second-order neurons: bipolar and horizontal cells. In mouse rods, there is a single presynaptic ribbon-type active zone ... Full text Link to item Cite

Downregulation of rhodopsin is an effective therapeutic strategy in ameliorating peripherin-2-associated inherited retinal disorders.

Journal Article Nat Commun · June 4, 2024 Given the absence of approved treatments for pathogenic variants in Peripherin-2 (PRPH2), it is imperative to identify a universally effective therapeutic target for PRPH2 pathogenic variants. To test the hypothesis that formation of the elongated discs in ... Full text Link to item Cite

ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims.

Journal Article Elife · November 22, 2023 Visual signal transduction takes place within a stack of flattened membranous 'discs' enclosed within the light-sensitive photoreceptor outer segment. The highly curved rims of these discs, formed in the process of disc enclosure, are fortified by large he ... Full text Link to item Cite

ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims.

Journal Article bioRxiv · August 29, 2023 Visual signal transduction takes place within a stack of flattened membranous "discs" enclosed within the light-sensitive photoreceptor outer segment. The highly curved rims of these discs, formed in the process of disc enclosure, are fortified by large he ... Full text Link to item Cite

Absolute Quantification of Photoreceptor Outer Segment Proteins.

Journal Article J Proteome Res · August 4, 2023 Photoreceptor cells generate neuronal signals in response to capturing light. This process, called phototransduction, takes place in a highly specialized outer segment organelle. There are significant discrepancies in the reported amounts of many proteins ... Full text Link to item Cite

Comparative study of PRPH2 D2 loop mutants reveals divergent disease mechanism in rods and cones.

Journal Article Cell Mol Life Sci · July 19, 2023 Mutations in the photoreceptor-specific tetraspanin gene peripherin-2 (PRPH2) lead to widely varying forms of retinal degeneration ranging from retinitis pigmentosa to macular dystrophy. Both inter- and intra-familial phenotypic heterogeneity has led to mu ... Full text Open Access Link to item Cite

Photoreceptor disc incisures form as an adaptive mechanism ensuring the completion of disc enclosure.

Journal Article Elife · July 14, 2023 The first steps of vision take place within a stack of tightly packed disc-shaped membranes, or 'discs', located in the outer segment compartment of photoreceptor cells. In rod photoreceptors, discs are enclosed inside the outer segment and contain deep in ... Full text Link to item Cite

Antagonizing the irreversible thrombomodulin-initiated proteolytic signaling alleviates age-related liver fibrosis via senescent cell killing.

Journal Article Cell Res · July 2023 Cellular senescence is a stress-induced, stable cell cycle arrest phenotype which generates a pro-inflammatory microenvironment, leading to chronic inflammation and age-associated diseases. Determining the fundamental molecular pathways driving senescence ... Full text Open Access Link to item Cite

Absolute quantification of photoreceptor outer segment proteins.

Journal Article bioRxiv · June 11, 2023 Photoreceptor cells generate neuronal signals in response to capturing light. This process, called phototransduction, takes place in a highly specialized outer segment organelle. There are significant discrepancies in the reported amounts of many proteins ... Full text Link to item Cite

Photoreceptor disc incisures form as an adaptive mechanism ensuring the completion of disc enclosure.

Journal Article bioRxiv · April 7, 2023 The first steps of vision take place within a stack of tightly packed disc-shaped membranes, or "discs", located in the outer segment compartment of photoreceptor cells. In rod photoreceptors, discs are enclosed inside the outer segment and contain deep in ... Full text Link to item Cite

The WAVE complex drives the morphogenesis of the photoreceptor outer segment cilium.

Journal Article Proc Natl Acad Sci U S A · March 21, 2023 The photoreceptor outer segment is a modified cilium filled with hundreds of flattened "disc" membranes responsible for efficient light capture. To maintain photoreceptor health and functionality, outer segments are continuously renewed through the additio ... Full text Link to item Cite

Nrl:CreERT2 mouse model to induce mosaic gene expression in rod photoreceptors.

Journal Article Front Mol Neurosci · 2023 Photoreceptors are sensory neurons that capture light within their outer segment, a narrow cylindrical organelle stacked with disc-shaped membranes housing the visual pigment. Photoreceptors are the most abundant neurons in the retina and are tightly packe ... Full text Link to item Cite

The Role of Peripherin-2/ROM1 Complexes in Photoreceptor Outer Segment Disc Morphogenesis.

Journal Article Adv Exp Med Biol · 2023 The light-sensitive outer segment organelle of photoreceptor cells contains a stack of hundreds of flat, disc-shaped membranes called discs. The rims of these discs contain a photoreceptor-specific tetraspanin protein peripherin-2 (also known as rds or PRP ... Full text Link to item Cite

A Ciliary Branched Actin Network Drives Photoreceptor Disc Morphogenesis.

Journal Article Adv Exp Med Biol · 2023 The light-detecting organelle of the photoreceptor cell is a modified primary cilium, called the outer segment. The outer segment houses hundreds of light-sensitive membrane, "discs," that are continuously renewed by the constant formation of new discs at ... Full text Link to item Cite

Microvesicle release from inner segments of healthy photoreceptors is a conserved phenomenon in mammalian species.

Journal Article Dis Model Mech · November 1, 2022 Many inherited visual diseases arise from mutations that affect the structure and function of photoreceptor cells. In some cases, the pathology is accompanied by a massive release of extracellular vesicles from affected photoreceptors. In this study, we ad ... Full text Link to item Cite

Apical CLC-2 in retinal pigment epithelium is crucial for survival of the outer retina.

Journal Article FASEB J · July 2021 Knockout of the chloride channel protein 2 (CLC-2; CLCN2) results in fast progressing blindness in mice. Retinal Pigment Epithelium (RPE) and photoreceptors undergo, in parallel, rapid, and profound morphological changes and degeneration. Immunohistochemis ... Full text Link to item Cite

Unusual mode of dimerization of retinitis pigmentosa-associated F220C rhodopsin.

Journal Article Sci Rep · May 18, 2021 Mutations in the G protein-coupled receptor (GPCR) rhodopsin are a common cause of autosomal dominant retinitis pigmentosa, a blinding disease. Rhodopsin self-associates in the membrane, and the purified monomeric apo-protein opsin dimerizes in vitro as it ... Full text Link to item Cite

Photoreceptor Disc Enclosure Is Tightly Controlled by Peripherin-2 Oligomerization.

Journal Article J Neurosci · April 21, 2021 Mutations in the PRPH2 gene encoding the photoreceptor-specific protein PRPH2 (also known as peripherin-2 or rds) cause a broad range of autosomal dominant retinal diseases. Most of these mutations affect the structure of the light-sensitive photoreceptor ... Full text Link to item Cite

The GARP Domain of the Rod CNG Channel's β1-Subunit Contains Distinct Sites for Outer Segment Targeting and Connecting to the Photoreceptor Disk Rim.

Journal Article J Neurosci · April 7, 2021 Vision begins when light is captured by the outer segment organelle of photoreceptor cells in the retina. Outer segments are modified cilia filled with hundreds of flattened disk-shaped membranes. Disk membranes are separated from the surrounding plasma me ... Full text Link to item Cite

Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract.

Journal Article Sci Rep · January 26, 2021 S100A4, a member of the S100 family of multifunctional calcium-binding proteins, participates in several physiological and pathological processes. In this study, we demonstrate that S100A4 expression is robustly induced in differentiating fiber cells of th ... Full text Open Access Link to item Cite

Deletion of the phosphatase INPP5E in the murine retina impairs photoreceptor axoneme formation and prevents disc morphogenesis.

Journal Article J Biol Chem · 2021 INPP5E, also known as pharbin, is a ubiquitously expressed phosphatidylinositol polyphosphate 5-phosphatase that is typically located in the primary cilia and modulates the phosphoinositide composition of membranes. Mutations to or loss of INPP5E is associ ... Full text Link to item Cite

TMEM67, TMEM237, and Embigin in Complex With Monocarboxylate Transporter MCT1 Are Unique Components of the Photoreceptor Outer Segment Plasma Membrane.

Journal Article Mol Cell Proteomics · 2021 The outer segment (OS) organelle of vertebrate photoreceptors is a highly specialized cilium evolved to capture light and initiate light response. The plasma membrane which envelopes the OS plays vital and diverse roles in supporting photoreceptor function ... Full text Link to item Cite

Highly photostable fluorescent labeling of proteins in live cells using exchangeable coiled coils heterodimerization.

Journal Article Cell Mol Life Sci · November 2020 Fluorescent proteins are commonly used to label target proteins in live cells. However, the conventional approach based on covalent fusion of targeted proteins with fluorescent protein probes is limited by the slow rate of fluorophore maturation and irretr ... Full text Link to item Cite

Photoreceptor Discs: Built Like Ectosomes.

Journal Article Trends Cell Biol · November 2020 The light-sensitive outer segment organelle of the vertebrate photoreceptor cell is a modified cilium filled with hundreds of flattened 'disc' membranes that provide vast light-absorbing surfaces. The outer segment is constantly renewed with new discs adde ... Full text Link to item Cite

Progressive optic atrophy in a retinal ganglion cell-specific mouse model of complex I deficiency.

Journal Article Sci Rep · October 1, 2020 Optic atrophy resulting from retinal ganglion cell (RGC) degeneration is a prominent ocular manifestation of mitochondrial dysfunction. Although transgenic mice lacking the mitochondrial complex I accessory subunit NDUFS4 develop early-onset optic atrophy, ... Full text Link to item Cite

Comprehensive identification of mRNA isoforms reveals the diversity of neural cell-surface molecules with roles in retinal development and disease.

Journal Article Nat Commun · July 3, 2020 Genes encoding cell-surface proteins control nervous system development and are implicated in neurological disorders. These genes produce alternative mRNA isoforms which remain poorly characterized, impeding understanding of how disease-associated mutation ... Full text Link to item Cite

Phosphoinositide Profile of the Mouse Retina.

Journal Article Cells · June 7, 2020 Phosphoinositides are known to play multiple roles in eukaryotic cells. Although dysregulation of phosphoinositide metabolism in the retina has been reported to cause visual dysfunction in animal models and human patients, our understanding of the phosphoi ... Full text Link to item Cite

Advancing Clinical Trials for Inherited Retinal Diseases: Recommendations from the Second Monaciano Symposium.

Journal Article Transl Vis Sci Technol · June 2020 Major advances in the study of inherited retinal diseases (IRDs) have placed efforts to develop treatments for these blinding conditions at the forefront of the emerging field of precision medicine. As a result, the growth of clinical trials for IRDs has i ... Full text Open Access Link to item Cite

Multimodal Coherent Imaging of Retinal Biomarkers of Alzheimer's Disease in a Mouse Model.

Journal Article Sci Rep · May 13, 2020 We acquired depth-resolved light scattering measurements from the retinas of triple transgenic Alzheimer's Disease (3xTg-AD) mice and wild type (WT) age-matched controls using co-registered angle-resolved low-coherence interferometry (a/LCI) and optical co ... Full text Link to item Cite

The F220C and F45L rhodopsin mutations identified in retinitis pigmentosa patients do not cause pathology in mice.

Journal Article Sci Rep · May 5, 2020 Retinitis pigmentosa is a retinal degenerative disease that leads to blindness through photoreceptor loss. Rhodopsin is the most frequently mutated protein in this disease. While many rhodopsin mutations have well-understood consequences that lead to cell ... Full text Link to item Cite

Probing Proteostatic Stress in Degenerating Photoreceptors Using Two Complementary In Vivo Reporters of Proteasomal Activity.

Journal Article eNeuro · 2020 Inherited retinal degenerations originate from mutations in >300 genes, many of which cause the production of misfolded mutant photoreceptor proteins that are ultimately degraded by the ubiquitin-proteasome system (UPS). It was previously shown that rod ph ... Full text Link to item Cite

Photoreceptor Disc Enclosure Occurs in the Absence of Normal Peripherin-2/rds Oligomerization.

Journal Article Front Cell Neurosci · 2020 Mutations in the peripherin-2 gene (PRPH2, also known as rds) cause a heterogeneous range of autosomal dominant retinal diseases. PRPH2 encodes a photoreceptor-specific tetraspanin protein, PRPH2, that is a main structural component of the photoreceptor ou ... Full text Link to item Cite

Photoreceptor disc membranes are formed through an Arp2/3-dependent lamellipodium-like mechanism.

Journal Article Proc Natl Acad Sci U S A · December 26, 2019 The light-sensitive outer segment of the vertebrate photoreceptor is a highly modified primary cilium filled with disc-shaped membranes that provide a vast surface for efficient photon capture. The formation of each disc is initiated by a ciliary membrane ... Full text Link to item Cite

Disrupted Blood-Retina Lysophosphatidylcholine Transport Impairs Photoreceptor Health But Not Visual Signal Transduction.

Journal Article J Neurosci · December 4, 2019 Retinal photoreceptor cells contain the highest concentration of docosahexaenoic acid (DHA) in our bodies, and it has been long assumed that this is critical for supporting normal vision. Indeed, early studies using DHA dietary restriction documented reduc ... Full text Link to item Cite

Photoreceptors in a mouse model of Leigh syndrome are capable of normal light-evoked signaling.

Journal Article J Biol Chem · August 16, 2019 Mitochondrial dysfunction is an important cause of heritable vision loss. Mutations affecting mitochondrial bioenergetics may lead to isolated vision loss or life-threatening systemic disease, depending on a mutation's severity. Primary optic nerve atrophy ... Full text Open Access Link to item Cite

How to build a photoreceptor disc?

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2019 Link to item Cite

PRCD supports the organized structure of the photoreceptor outer segment

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2019 Link to item Cite

Ciliary Delivery of the CNG-gated Channel in Rod Photoreceptors

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2019 Link to item Cite

PRCD is essential for high-fidelity photoreceptor disc formation.

Journal Article Proc Natl Acad Sci U S A · June 25, 2019 Progressive rod-cone degeneration (PRCD) is a small protein residing in the light-sensitive disc membranes of the photoreceptor outer segment. Until now, the function of PRCD has remained enigmatic despite multiple demonstrations that its mutations cause b ... Full text Link to item Cite

Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration.

Journal Article Immunity · March 19, 2019 Microglia from different nervous system regions are molecularly and anatomically distinct, but whether they also have different functions is unknown. We combined lineage tracing, single-cell transcriptomics, and electrophysiology of the mouse retina and sh ... Full text Link to item Cite

PRCD Is a Small Disc-Specific Rhodopsin-Binding Protein of Unknown Function.

Journal Article Adv Exp Med Biol · 2019 PRCD (progressive rod-cone degeneration) is a small ~6 kDa protein with unknown function that specifically resides in photoreceptor discs and interacts with rhodopsin. PRCD's discovery resulted from decades-long study of a canine retinal disease called pro ... Full text Link to item Cite

Increased proteasomal activity supports photoreceptor survival in inherited retinal degeneration.

Journal Article Nat Commun · April 30, 2018 Inherited retinal degenerations, affecting more than 2 million people worldwide, are caused by mutations in over 200 genes. This suggests that the most efficient therapeutic strategies would be mutation independent, i.e., targeting common pathological cond ... Full text Open Access Link to item Cite

C8ORF37 Is Required for Photoreceptor Outer Segment Disc Morphogenesis by Maintaining Outer Segment Membrane Protein Homeostasis.

Journal Article J Neurosci · March 28, 2018 C8ORF37 is a causative gene for three different clinical forms of incurable retinal degeneration. However, the completely unknown function of C8ORF37 limits our understanding of the pathogenicity of C8ORF37 mutations. Here, we performed a comprehensive phe ... Full text Link to item Cite

Dopamine-Dependent Sensitization of Rod Bipolar Cells by GABA Is Conveyed through Wide-Field Amacrine Cells.

Journal Article J Neurosci · January 17, 2018 The vertebrate retina has the remarkable ability to support visual function under conditions of limited illumination, including the processing of signals evoked by single photons. Dim-light vision is regulated by several adaptive mechanisms. The mechanism ... Full text Link to item Cite

Transducin β-Subunit Can Interact with Multiple G-Protein γ-Subunits to Enable Light Detection by Rod Photoreceptors.

Journal Article eNeuro · 2018 The heterotrimeric G-protein transducin mediates visual signaling in vertebrate photoreceptor cells. Many aspects of the function of transducin were learned from knock-out mice lacking its individual subunits. Of particular interest is the knockout of its ... Full text Open Access Link to item Cite

An increase in proteolytic capacity delays photoreceptor loss in retinal degeneration

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2017 Link to item Cite

Photoreceptor discs form through peripherin-dependent suppression of ciliary ectosome release.

Journal Article J Cell Biol · May 1, 2017 The primary cilium is a highly conserved organelle housing specialized molecules responsible for receiving and processing extracellular signals. A recently discovered property shared across many cilia is the ability to release small vesicles called ectosom ... Full text Link to item Cite

Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration.

Journal Article PLoS Genet · April 2017 Arf4 is proposed to be a critical regulator of membrane protein trafficking in early secretory pathway. More recently, Arf4 was also implicated in regulating ciliary trafficking, however, this has not been comprehensively tested in vivo. To directly addres ... Full text Link to item Cite

Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants.

Journal Article Nat Commun · October 3, 2016 Retinitis pigmentosa (RP) is a blinding disease often associated with mutations in rhodopsin, a light-sensing G protein-coupled receptor and phospholipid scramblase. Most RP-associated mutations affect rhodopsin's activity or transport to disc membranes. I ... Full text Link to item Cite

Progressive Rod-Cone Degeneration (PRCD) Protein Requires N-Terminal S-Acylation and Rhodopsin Binding for Photoreceptor Outer Segment Localization and Maintaining Intracellular Stability.

Journal Article Biochemistry · September 13, 2016 The light-sensing outer segments of photoreceptor cells harbor hundreds of flattened membranous discs containing the visual pigment, rhodopsin, and all the proteins necessary for visual signal transduction. PRCD (progressive rod-cone degeneration) protein ... Full text Link to item Cite

Analyzing spatial correlations in tissue using angle-resolved low coherence interferometry measurements guided by co-located optical coherence tomography.

Journal Article Biomed Opt Express · April 1, 2016 Angle-resolved low coherence interferometry (a/LCI) is an optical technique used to measure nuclear morphology in situ. However, a/LCI is not an imaging modality and can produce ambiguous results when the measurements are not properly oriented to the tissu ... Full text Link to item Cite

Guanylate cyclase 1 relies on rhodopsin for intracellular stability and ciliary trafficking.

Journal Article Elife · November 21, 2015 Sensory cilia are populated by a select group of signaling proteins that detect environmental stimuli. How these molecules are delivered to the sensory cilium and whether they rely on one another for specific transport remains poorly understood. Here, we i ... Full text Link to item Cite

Discs of mammalian rod photoreceptors form through the membrane evagination mechanism.

Journal Article J Cell Biol · November 9, 2015 Photoreceptor discs are membrane organelles harboring components of the visual signal transduction pathway. The mechanism by which discs form remains enigmatic and is the subject of a major controversy. Classical studies suggest that discs are formed as se ... Full text Link to item Cite

Introducing Kirill A. Martemyanov, the 2014 recipient of the Cogan Award.

Journal Article Invest Ophthalmol Vis Sci · December 15, 2014 Full text Link to item Cite

R9AP targeting to rod outer segments is independent of rhodopsin and is guided by the SNARE homology domain.

Journal Article Mol Biol Cell · September 1, 2014 In vertebrate photoreceptor cells, rapid recovery from light excitation is dependent on the RGS9â‹…Gβ5 GTPase-activating complex located in the light-sensitive outer segment organelle. RGS9â‹…Gβ5 is tethered to the outer segment membranes by its membrane ancho ... Full text Link to item Cite

Automatic segmentation of up to ten layer boundaries in SD-OCT images of the mouse retina with and without missing layers due to pathology.

Journal Article Biomed Opt Express · February 1, 2014 Accurate quantification of retinal layer thicknesses in mice as seen on optical coherence tomography (OCT) is crucial for the study of numerous ocular and neurological diseases. However, manual segmentation is time-consuming and subjective. Previous attemp ... Full text Link to item Cite

Current understanding of signal amplification in phototransduction.

Journal Article Cell Logist · 2014 The studies of visual signal transduction, or phototransduction, have played a pivotal role in elucidating the most general principles of G protein signaling, particularly in regards to the concept of signal amplification, i.e., the process by which activa ... Full text Link to item Cite

The role of dopamine in fine-tuning cone- and rod-driven vision

Chapter · January 1, 2014 Dopamine, one of the major neuromodulators in the retina, acts through dopamine D1, D2, and D4 G-protein-coupled receptors localized to many types of retinal neurons. This expansive expression pattern allows dopamine to regulate visual processing at differ ... Full text Cite

Timing is everything: GTPase regulation in phototransduction.

Journal Article Invest Ophthalmol Vis Sci · November 21, 2013 As the molecular mechanisms of vertebrate phototransduction became increasingly clear in the 1980s, a persistent problem was the discrepancy between the slow GTP hydrolysis catalyzed by the phototransduction G protein, transducin, and the much more rapid p ... Full text Link to item Cite

Proteasome overload is a common stress factor in multiple forms of inherited retinal degeneration.

Journal Article Proc Natl Acad Sci U S A · June 11, 2013 Inherited retinal degenerations, caused by mutations in over 100 individual genes, affect approximately 2 million people worldwide. Many of the underlying mutations cause protein misfolding or mistargeting in affected photoreceptors. This places an increas ... Full text Link to item Cite

Proteomic identification of unique photoreceptor disc components reveals the presence of PRCD, a protein linked to retinal degeneration.

Journal Article J Proteome Res · June 7, 2013 Visual signal transduction takes place on the surface of flat membrane vesicles called photoreceptor discs, which reside inside the light-sensitive outer segment organelle of vertebrate photoreceptor cells. Although biochemical studies have indicated that ... Full text Link to item Cite

Absence of synaptic regulation by phosducin in retinal slices.

Journal Article PLoS One · 2013 Phosducin is an abundant photoreceptor protein that binds G-protein βγ subunits and plays a role in modulating synaptic transmission at photoreceptor synapses under both dark-adapted and light-adapted conditions in vivo. To examine the role of phosducin at ... Full text Link to item Cite

A single valine residue plays an essential role in peripherin/rds targeting to photoreceptor outer segments.

Journal Article PLoS One · 2013 Peripherin/retinal degeneration slow (rds) is an integral membrane protein specifically localized to the light-sensing organelle of the photoreceptor cell, the outer segment. Within the outer segment, peripherin is found at the edges of photoreceptor discs ... Full text Link to item Cite

Regulator of G-protein signaling-21 (RGS21) is an inhibitor of bitter gustatory signaling found in lingual and airway epithelia.

Journal Article J Biol Chem · December 7, 2012 The gustatory system detects tastants and transmits signals to the brain regarding ingested substances and nutrients. Although tastant receptors and taste signaling pathways have been identified, little is known about their regulation. Because bitter, swee ... Full text Link to item Cite

The relationship between slow photoresponse recovery rate and temporal resolution of vision.

Journal Article J Neurosci · October 10, 2012 The rate at which photoreceptors recover from excitation is thought to be critical for setting the temporal resolution of vision. Indeed, mutations in RGS9 (regulator of G-protein signaling 9) and R9AP (RGS9 anchor protein) proteins mediating rapid photore ... Full text Link to item Cite

CNG-modulin: a novel Ca-dependent modulator of ligand sensitivity in cone photoreceptor cGMP-gated ion channels.

Journal Article J Neurosci · February 29, 2012 The transduction current in several different types of sensory neurons arises from the activity of cyclic nucleotide-gated (CNG) ion channels. The channels in these sensory neurons vary in structure and function, yet each one demonstrates calcium-dependent ... Full text Link to item Cite

Photoreceptor signaling: supporting vision across a wide range of light intensities.

Journal Article J Biol Chem · January 13, 2012 Featured Publication For decades, photoreceptors have been an outstanding model system for elucidating basic principles in sensory transduction and biochemistry and for understanding many facets of neuronal cell biology. In recent years, new knowledge of the kinetics of signal ... Full text Link to item Cite

Membrane attachment is key to protecting transducin GTPase-activating complex from intracellular proteolysis in photoreceptors.

Journal Article J Neurosci · October 12, 2011 Featured Publication The members of the R7 regulator of G-protein signaling (RGS) protein subfamily are versatile regulators of G-protein signaling throughout the nervous system. Recent studies indicate that they are often found in complexes with membrane anchor proteins that ... Full text Link to item Cite

Rod vision is controlled by dopamine-dependent sensitization of rod bipolar cells by GABA.

Journal Article Neuron · October 6, 2011 Featured Publication Dark and light adaptation of retinal neurons allow our vision to operate over an enormous light intensity range. Here we report a mechanism that controls the light sensitivity and operational range of rod-driven bipolar cells that mediate dim-light vision. ... Full text Link to item Cite

Integrating energy calculations with functional assays to decipher the specificity of G protein-RGS protein interactions.

Journal Article Nat Struct Mol Biol · June 19, 2011 Featured Publication The diverse Regulator of G protein Signaling (RGS) family sets the timing of G protein signaling. To understand how the structure of RGS proteins determines their common ability to inactivate G proteins and their selective G protein recognition, we combine ... Full text Link to item Cite

Phosphorylation of G protein-coupled receptor kinase 1 (GRK1) is regulated by light but independent of phototransduction in rod photoreceptors.

Journal Article J Biol Chem · June 10, 2011 Phosphorylation of rhodopsin by G protein-coupled receptor kinase 1 (GRK1, or rhodopsin kinase) is critical for the deactivation of the phototransduction cascade in vertebrate photoreceptors. Based on our previous studies in vitro, we predicted that Ser(21 ... Full text Link to item Cite

Proteomic profiling of a layered tissue reveals unique glycolytic specializations of photoreceptor cells.

Journal Article Mol Cell Proteomics · March 2011 Featured Publication The retina is a highly ordered tissue whose outermost layers are formed by subcellular compartments of photoreceptors generating light-evoked electrical responses. We studied protein distributions among individual photoreceptor compartments by separating t ... Full text Link to item Cite

RGS9 knockout causes a short delay in light responses of ON-bipolar cells.

Journal Article PLoS One · 2011 RGS9 and R9AP are components of the photoreceptor-specific GTPase activating complex responsible for rapid inactivation of the G protein, transducin, in the course of photoresponse recovery from excitation. The amount of this complex in photoreceptors is s ... Full text Link to item Cite

Facilitative glucose transporter Glut1 is actively excluded from rod outer segments.

Journal Article J Cell Sci · November 1, 2010 Photoreceptors are among the most metabolically active cells in the body, relying on both oxidative phosphorylation and glycolysis to satisfy their high energy needs. Local glycolysis is thought to be particularly crucial in supporting the function of the ... Full text Open Access Link to item Cite

Heparan sulfate, including that in Bruch's membrane, inhibits the complement alternative pathway: implications for age-related macular degeneration.

Journal Article J Immunol · November 1, 2010 An imbalance between activation and inhibition of the complement system has been implicated in the etiologies of numerous common diseases. Allotypic variants of a key complement fluid-phase regulatory protein, complement factor H (CFH), are strongly associ ... Full text Link to item Cite

Mechanistic basis for the failure of cone transducin to translocate: why cones are never blinded by light.

Journal Article J Neurosci · May 19, 2010 Featured Publication The remarkable ability of our vision to function under ever-changing conditions of ambient illumination is mediated by multiple molecular mechanisms regulating the light sensitivity of rods and cones. One such mechanism involves massive translocation of si ... Full text Link to item Cite

Phosducin regulates transmission at the photoreceptor-to-ON-bipolar cell synapse.

Journal Article J Neurosci · March 3, 2010 The rate of synaptic transmission between photoreceptors and bipolar cells has been long known to depend on conditions of ambient illumination. However, the molecular mechanisms that mediate and regulate transmission at this ribbon synapse are poorly under ... Full text Link to item Cite

Vision: the retinoid cycle in Drosophila.

Journal Article Curr Biol · February 9, 2010 It was commonly accepted that the enzymatic pathway regenerating bleached visual pigments is present in vertebrate but not invertebrate animals. New studies indicate that this pathway is present in Drosophila and is vital for maintaining both the amount of ... Full text Link to item Cite

Light-driven translocation of signaling proteins in vertebrate photoreceptors

Chapter · January 1, 2010 Sustained illumination causes massive translocation of at least three signal transduction proteins (transducin, arrestin, and recoverin) into and out of the outer segment compartment of rod and cone photoreceptors. This phenomenon is thought to contribute ... Full text Cite

Light-driven translocation of signaling proteins in vertebrate photoreceptors

Chapter · January 1, 2010 Sustained illumination causes massive translocation of at least three signal transduction proteins (transducin, arrestin, and recoverin) into and out of the outer segment compartment of rod and cone photoreceptors. This phenomenon is thought to contribute ... Full text Cite

Growth factor receptor-bound protein 14 undergoes light-dependent intracellular translocation in rod photoreceptors: functional role in retinal insulin receptor activation.

Journal Article Biochemistry · June 23, 2009 Growth factor receptor-bound protein 14 (Grb14) is involved in growth factor receptor tyrosine kinase signaling. Here we report that light causes a major redistribution of Grb14 among the individual subcellular compartments of the retinal rod photoreceptor ... Full text Link to item Cite

Rapid and sensitive method for detection of Y402, H402, I62, and V62 variants of complement factor H in human plasma samples using mass spectrometry.

Journal Article Invest Ophthalmol Vis Sci · April 2009 PURPOSE: Variations in the complement factor H (CFH) gene are tightly associated with age-related macular degeneration (AMD) across diverse populations. Of the many nonsynonymous coding variants in CFH, two are most strongly associated with increased risk ... Full text Link to item Cite

Ankyrin-G promotes cyclic nucleotide-gated channel transport to rod photoreceptor sensory cilia.

Journal Article Science · March 20, 2009 Cyclic nucleotide-gated (CNG) channels localize exclusively to the plasma membrane of photosensitive outer segments of rod photoreceptors where they generate the electrical response to light. Here, we report the finding that targeting of CNG channels to th ... Full text Link to item Cite

Biology and functions of the RGS9 isoforms.

Chapter · 2009 Two splice isoforms of the ninth member of the regulator of G protein signaling (RGS) protein family are expressed in the nervous system, where they are engaged in such diverse functions as vision and behavior. RGS9-1 regulates phototransduction in rods an ... Full text Link to item Cite

Functional comparison of RGS9 splice isoforms in a living cell.

Journal Article Proc Natl Acad Sci U S A · December 30, 2008 Featured Publication Two isoforms of the GTPase-activating protein, regulator of G protein signaling 9 (RGS9), control such fundamental functions as vision and behavior. RGS9-1 regulates phototransduction in rods and cones, and RGS9-2 regulates dopamine and opioid signaling in ... Full text Link to item Cite

Electrostatic and lipid anchor contributions to the interaction of transducin with membranes: mechanistic implications for activation and translocation.

Journal Article J Biol Chem · November 7, 2008 The heterotrimeric G protein transducin is a key component of the vertebrate phototransduction cascade. Transducin is peripherally attached to membranes of the rod outer segment, where it interacts with other proteins at the membrane-cytosol interface. How ... Full text Link to item Cite

The outer segment serves as a default destination for the trafficking of membrane proteins in photoreceptors.

Journal Article J Cell Biol · November 3, 2008 Featured Publication Photoreceptors are compartmentalized neurons in which all proteins responsible for evoking visual signals are confined to the outer segment. Yet, the mechanisms responsible for establishing and maintaining photoreceptor compartmentalization are poorly unde ... Full text Link to item Cite

Direct allosteric regulation between the GAF domain and catalytic domain of photoreceptor phosphodiesterase PDE6.

Journal Article J Biol Chem · October 31, 2008 Photoreceptor cGMP phosphodiesterase (PDE6) is the central enzyme in the visual transduction cascade. The PDE6 catalytic subunit contains a catalytic domain and regulatory GAF domains. Unlike most GAF domain-containing cyclic nucleotide phosphodiesterases, ... Full text Link to item Cite

Transducin gamma-subunit sets expression levels of alpha- and beta-subunits and is crucial for rod viability.

Journal Article J Neurosci · March 26, 2008 Transducin is a prototypic heterotrimeric G-protein mediating visual signaling in vertebrate photoreceptor cells. Despite its central role in phototransduction, little is known about the mechanisms that regulate its expression and maintain approximately st ... Full text Link to item Cite

Phosducin regulates the expression of transducin betagamma subunits in rod photoreceptors and does not contribute to phototransduction adaptation.

Journal Article J Gen Physiol · September 2007 For over a decade, phosducin's interaction with the betagamma subunits of the G protein, transducin, has been thought to contribute to light adaptation by dynamically controlling the amount of transducin heterotrimer available for activation by photoexcite ... Full text Link to item Cite

Oxidative stress-induced expression and modulation of Phosphatase of Regenerating Liver-1 (PRL-1) in mammalian retina.

Journal Article Biochim Biophys Acta · September 2007 The phosphatase of regenerating liver-1, PRL-1, gene was detected in a screen for foveal cone photoreceptor-associated genes. It encodes a small protein tyrosine phosphatase that was previously immunolocalized to the photoreceptors in primate retina. Here ... Full text Link to item Cite

Structure and function of the visual arrestin oligomer.

Journal Article EMBO J · March 21, 2007 A distinguishing feature of rod arrestin is its ability to form oligomers at physiological concentrations. Using visible light scattering, we show that rod arrestin forms tetramers in a cooperative manner in solution. To investigate the structure of the te ... Full text Link to item Cite

Transducin translocation in rods is triggered by saturation of the GTPase-activating complex.

Journal Article J Neurosci · January 31, 2007 Light causes massive translocation of G-protein transducin from the light-sensitive outer segment compartment of the rod photoreceptor cell. Remarkably, significant translocation is observed only when the light intensity exceeds a critical threshold level. ... Full text Link to item Cite

Light-driven translocation of signaling proteins in vertebrate photoreceptors.

Journal Article Trends Cell Biol · November 2006 The dynamic localization of proteins within cells is often determined by environmental stimuli. In retinal photoreceptors, light exposure results in the massive translocation of three key signal transduction proteins, transducin, arrestin and recoverin, in ... Full text Link to item Cite

Minimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer.

Journal Article Biochemistry · September 26, 2006 G-proteins cycle between an inactive GDP-bound state and an active GTP-bound state, serving as molecular switches that coordinate cellular signaling. We recently used phage display to identify a series of peptides that bind G alpha subunits in a nucleotide ... Full text Link to item Cite

Kinetic mechanism of RGS9-1 potentiation by R9AP.

Journal Article Biochemistry · September 5, 2006 The duration of the photoreceptor's response to a light stimulus determines the speed at which an animal adjusts to ever-changing conditions of the visual environment. One critical component which regulates the photoresponse duration on the molecular level ... Full text Link to item Cite

RGS expression rate-limits recovery of rod photoresponses.

Journal Article Neuron · August 17, 2006 Signaling through G protein-coupled receptors (GPCRs) underlies many cellular processes, yet it is not known which molecules determine the duration of signaling in intact cells. Two candidates are G protein-coupled receptor kinases (GRKs) and Regulators of ... Full text Link to item Cite

The N terminus of GTP gamma S-activated transducin alpha-subunit interacts with the C terminus of the cGMP phosphodiesterase gamma-subunit.

Journal Article J Biol Chem · March 10, 2006 Dynamic regulation of G-protein signaling in the phototransduction cascade ensures the high temporal resolution of vision. In a key step, the activated alpha-subunit of transducin (Galphat-GTP) activates the cGMP phosphodiesterase (PDE) by binding the inhi ... Full text Link to item Cite

Arrestin translocation is induced at a critical threshold of visual signaling and is superstoichiometric to bleached rhodopsin.

Journal Article J Neurosci · January 25, 2006 Light induces massive translocation of major signaling proteins between the subcellular compartments of photoreceptors. Among them is visual arrestin responsible for quenching photoactivated rhodopsin, which moves into photoreceptor outer segments during i ... Full text Link to item Cite

Beyond counting photons: trials and trends in vertebrate visual transduction.

Journal Article Neuron · November 3, 2005 For over 30 years, photoreceptors have been an outstanding model system for elucidating basic principles in sensory transduction and G protein signaling. Recently, photoreceptors have become an equally attractive model for studying many facets of neuronal ... Full text Link to item Cite

Recoverin undergoes light-dependent intracellular translocation in rod photoreceptors.

Journal Article J Biol Chem · August 12, 2005 Photoreceptor cells have a remarkable capacity to adapt the sensitivity and speed of their responses to ever changing conditions of ambient illumination. Recent studies have revealed that a major contributor to this adaptation is the phenomenon of light-dr ... Full text Link to item Cite

Recoverin improves rod-mediated vision by enhancing signal transmission in the mouse retina.

Journal Article Neuron · May 5, 2005 Vision in dim light requires that photons absorbed by rod photoreceptors evoke signals that reliably propagate through the retina. We investigated how a perturbation in rod physiology affects propagation of those signals in the retina and ultimately visual ... Full text Link to item Cite

R7BP, a novel neuronal protein interacting with RGS proteins of the R7 family.

Journal Article J Biol Chem · February 18, 2005 The R7 subfamily of the regulators of G protein signaling (RGS) proteins is represented by four members broadly expressed in the mammalian nervous system. Here we report that in the brain all four R7 proteins form tight complexes with a previously unidenti ... Full text Link to item Cite

Sulfhydryl-reactive, cleavable, and radioiodinatable benzophenone photoprobes for study of protein-protein interaction.

Journal Article Bioconjug Chem · 2005 The major task in proteomics is to understand how proteins interact with their partners. The photo-cross-linking technique enables direct probing of protein-protein interaction. Here we report the development of three novel sulfhydryl-reactive benzophenone ... Full text Link to item Cite

Phosducin regulates the level of transducin expression in rod photoreceptors

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · January 1, 2005 Link to item Cite

Myosin III illuminates the mechanism of arrestin translocation.

Journal Article Neuron · July 8, 2004 Recent studies have revealed that light adaptation of both vertebrate and invertebrate photoreceptors is accompanied by massive translocations of major signaling proteins in and out of the cellular compartments where visual signal transduction takes place. ... Full text Link to item Cite

Phosducin facilitates light-driven transducin translocation in rod photoreceptors. Evidence from the phosducin knockout mouse.

Journal Article J Biol Chem · April 30, 2004 Phosducin is a photoreceptor-specific protein known to interact with the beta gamma subunits of G proteins. In pursuit of the function of phosducin, we tested the hypothesis that it regulates the light-driven translocation of G protein transducin from the ... Full text Link to item Cite

Quantification of light-dependent arrestin translocation in mouse rod photoreceptors

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2004 Link to item Cite

Absence of the RGS9.Gbeta5 GTPase-activating complex in photoreceptors of the R9AP knockout mouse.

Journal Article J Biol Chem · January 16, 2004 Timely termination of the light response in retinal photoreceptors requires rapid inactivation of the G protein transducin. This is achieved through the stimulation of transducin GTPase activity by the complex of the ninth member of the regulator of G prot ... Full text Link to item Cite

Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation.

Journal Article Nature · January 1, 2004 The RGS proteins are GTPase activating proteins that accelerate the deactivation of G proteins in a variety of signalling pathways in eukaryotes. RGS9 deactivates the G proteins (transducins) in the rod and cone phototransduction cascades. It is anchored t ... Full text Link to item Cite

Kinetic approaches to study the function of RGS9 isoforms.

Journal Article Methods Enzymol · 2004 The experimental strategies developed in kinetic studies of interactions between RGS9 isoforms with G proteins of the Gi subfamily provide a useful framework for conducting similar studies with essentially any regulator of G-protein signaling (RGS) protein ... Full text Link to item Cite

The DEP domain determines subcellular targeting of the GTPase activating protein RGS9 in vivo.

Journal Article J Neurosci · November 12, 2003 DEP (for Disheveled, EGL-10, Pleckstrin) homology domains are present in numerous signaling proteins, including many in the nervous system, but their function remains mostly elusive. We report that the DEP domain of a photoreceptor-specific signaling prote ... Full text Link to item Cite

Protein translocation in photoreceptor light adaptation: a common theme in vertebrate and invertebrate vision.

Journal Article Sci STKE · October 14, 2003 How do our eyes adjust to daily light levels that vary by almost 11 orders of magnitude? Research shows that, in both vertebrates and invertebrates, signaling proteins are translocated in a light-dependent manner between the photoreceptor cellular compartm ... Full text Link to item Cite

Specificity of G protein-RGS protein recognition is regulated by affinity adapters.

Journal Article Neuron · June 19, 2003 RGS proteins regulate the duration of cell signaling by modulating the lifetime of activated G proteins. The specificity of RGS-G protein mutual recognition is critical for meeting unique timing requirements of numerous G protein-mediated pathways. Our stu ... Full text Link to item Cite

RPGR isoforms in photoreceptor connecting cilia and the transitional zone of motile cilia.

Journal Article Invest Ophthalmol Vis Sci · June 2003 PURPOSE: The retinitis pigmentosa guanosine triphosphatase (GTPase) regulator (RPGR) is essential for photoreceptor survival. There is as yet no consensus concerning the subcellular localization of RPGR. This study was undertaken as a comprehensive effort ... Full text Link to item Cite

R9AP regulates the activity of RGS9-GB5 and targets its localization in vivo

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · May 1, 2003 Link to item Cite

Ubiquitylation of the transducin betagamma subunit complex. Regulation by phosducin.

Journal Article J Biol Chem · November 15, 2002 G proteins (Galphabetagamma) are essential signaling molecules, which dissociate into Galpha and Gbetagamma upon activation by heptahelical membrane receptors. We have identified the betagamma subunit complex of the photoreceptor-specific G protein, transd ... Full text Link to item Cite

Like night and day: rods and cones have different pigment regeneration pathways.

Journal Article Neuron · September 26, 2002 Sustained vision requires continuous regeneration of visual pigments in rod and cone photoreceptors by the 11-cis-retinal chromophore. In this issue of Neuron, Mata et al. report a novel enzymatic pathway uniquely designed to keep up with the high demand f ... Full text Link to item Cite

Noncatalytic domains of RGS9-1.Gbeta 5L play a decisive role in establishing its substrate specificity.

Journal Article J Biol Chem · September 6, 2002 The complex between the photoreceptor-specific regulator of G protein signaling (RGS) protein, RGS9-1, and type 5 G protein beta-subunit, Gbeta5L, regulates the duration of the cellular response to light by stimulating the GTPase activity of G protein, tra ... Full text Link to item Cite

Specific binding of RGS9-Gbeta 5L to protein anchor in photoreceptor membranes greatly enhances its catalytic activity.

Journal Article J Biol Chem · July 5, 2002 The complex between the short splice variant of the ninth member of the RGS protein family and the long splice variant of type 5 G protein beta subunit (RGS9-Gbeta5L) plays a critical role in regulating the duration of the light response in vertebrate phot ... Full text Link to item Cite

Transducin-phosducin interactions in rod inner segments of the light-adapted rat

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · May 1, 2002 Link to item Cite

The identification of the inhibitory gamma-subunits of the type 6 retinal cyclic guanosine monophosphate phosphodiesterase in non-retinal tissues: differential processing of mRNA transcripts.

Journal Article Genomics · April 2002 Here, we report that mouse lung expresses gamma-subunit (PDEgamma) transcripts of the rod and cone photoreceptor cGMP phosphodiesterase genes (Pde6g and Pde6h, respectively). Moreover, a major 14-kDa protein (p14) in lung membranes was immunostained with a ... Full text Link to item Cite

Massive light-driven translocation of transducin between the two major compartments of rod cells: a novel mechanism of light adaptation.

Journal Article Neuron · March 28, 2002 We report a new cellular mechanism of rod photoreceptor adaptation in vivo, which is triggered by daylight levels of illumination. The mechanism involves a massive light-dependent translocation of the photoreceptor-specific G protein, transducin, between t ... Full text Link to item Cite

Rhodopsin phosphorylation: from terminating single photon responses to photoreceptor dark adaptation.

Journal Article Trends Neurosci · March 2002 Rhodopsin phosphorylation has provided one of the first examples of the ubiquitous regulatory pattern of specific kinases downregulating the activity of G-protein-coupled receptors. However, only recently have studies in living animals allowed us to consid ... Full text Link to item Cite

Two temporal phases of light adaptation in retinal rods.

Journal Article J Gen Physiol · February 2002 Vertebrate rod photoreceptors adjust their sensitivity as they adapt during exposure to steady light. Light adaptation prevents the rod from saturating and significantly extends its dynamic range. We examined the time course of the onset of light adaptatio ... Full text Link to item Cite

G proteins and phototransduction.

Journal Article Annu Rev Physiol · 2002 Phototransduction is the process by which a photon of light captured by a molecule of visual pigment generates an electrical response in a photoreceptor cell. Vertebrate rod phototransduction is one of the best-studied G protein signaling pathways. In this ... Full text Link to item Cite

RGS9-G beta 5 substrate selectivity in photoreceptors. Opposing effects of constituent domains yield high affinity of RGS interaction with the G protein-effector complex.

Journal Article J Biol Chem · October 5, 2001 RGS proteins regulate the duration of G protein signaling by increasing the rate of GTP hydrolysis on G protein alpha subunits. The complex of RGS9 with type 5 G protein beta subunit (G beta 5) is abundant in photoreceptors, where it stimulates the GTPase ... Full text Link to item Cite

Massive light-dependent movement of transducin from the outer segments of vertebrate rods.

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · March 15, 2001 Link to item Cite

The effector enzyme regulates the duration of G protein signaling in vertebrate photoreceptors by increasing the affinity between transducin and RGS protein.

Journal Article J Biol Chem · October 20, 2000 The photoreceptor-specific G protein transducin acts as a molecular switch, stimulating the activity of its downstream effector in its GTP-bound form and inactivating the effector upon GTP hydrolysis. This activity makes the rate of transducin GTPase an es ... Full text Link to item Cite

The gain of rod phototransduction: reconciliation of biochemical and electrophysiological measurements.

Journal Article Neuron · September 2000 We have resolved a central and long-standing paradox in understanding the amplification of rod phototransduction by making direct measurements of the gains of the underlying enzymatic amplifiers. We find that under optimized conditions a single photoisomer ... Full text Link to item Cite

The role of G protein beta 5 subunit in regulating transducin GTPase.

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · March 15, 2000 Link to item Cite

Signal amplification in the phototransduction cascade: New insights.

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · March 15, 2000 Link to item Cite

The GTPase activating factor for transducin in rod photoreceptors is the complex between RGS9 and type 5 G protein beta subunit.

Journal Article Proc Natl Acad Sci U S A · March 2, 1999 Proteins of the regulators of G protein signaling (RGS) family modulate the duration of intracellular signaling by stimulating the GTPase activity of G protein alpha subunits. It has been established that the ninth member of the RGS family (RGS9) participa ... Full text Link to item Cite

Interaction sites of the C-terminal region of the cGMP phosphodiesterase inhibitory subunit with the GDP-bound transducin alpha-subunit.

Journal Article Biochem J · January 15, 1999 In the present report, the region of interaction between the GDP-bound alpha-subunit of transducin (alphat.GTP) and the cGMP phosphodiesterase inhibitory gamma-subunit (Pgamma) has been studied. It is widely accepted that the alphat.GTP is the active form ... Link to item Cite

Role for the target enzyme in deactivation of photoreceptor G protein in vivo.

Journal Article Science · October 2, 1998 Heterotrimeric guanosine 5'-triphosphate (GTP)-binding proteins (G proteins) are deactivated by hydrolysis of the GTP that they bind when activated by transmembrane receptors. Transducin, the G protein that relays visual excitation from rhodopsin to the cy ... Full text Link to item Cite

Onset of feedback reactions underlying vertebrate rod photoreceptor light adaptation.

Journal Article J Gen Physiol · January 1998 Light adaptation in vertebrate photoreceptors is thought to be mediated through a number of biochemical feedback reactions that reduce the sensitivity of the photoreceptor and accelerate the kinetics of the photoresponse. Ca2+ plays a major role in this pr ... Full text Link to item Cite

Photoreceptor phosphodiesterase: interaction of inhibitory gamma subunit and cyclic GMP with specific binding sites on catalytic subunits.

Journal Article Methods · January 1998 The photoreceptor phosphodiesterase (PDE6) is the central effector enzyme in the phototransduction cascade of photoreceptor cells. It is the only known PDE isoform the activity of which is regulated by interaction with a heterotrimeric G protein. The rod P ... Full text Link to item Cite

The gamma-subunit of the rod photoreceptor cGMP-binding cGMP-specific PDE is expressed in mouse lung.

Journal Article Cell Biochem Biophys · 1998 The type 6 phosphodiesterase (PDE-6) from retinal rod photoreceptors is an alpha beta gamma 2 heterotetramer. The alpha- and beta-subunits contain catalytic sites for cGMP hydrolysis, whereas the gamma-subunits (P gamma) serve as a protein inhibitor of the ... Full text Link to item Cite

Onset rates of three feedback reactions that are considered to underlie light adaptation in frog rods

Conference Investigative Ophthalmology and Visual Science · December 1, 1997 Purpose. Light adaptation in rod photoreceptors is thought to be mediated by a number of feedback reactions which cause the photoresponse to become faster and less sensitive. We evaluated how fast the changes in two intracellular second messengers, Ca and ... Cite

The regulation of the cGMP-binding cGMP phosphodiesterase by proteins that are immunologically related to gamma subunit of the photoreceptor cGMP phosphodiesterase.

Journal Article J Biol Chem · July 18, 1997 The cGMP phosphodiesterase from retinal rods (PDE-6) is an alphabetagamma2 heterotetramer. The alpha and beta subunits contain catalytic sites for cGMP hydrolysis, whereas the gamma subunits serve as a protein inhibitor of the enzyme. Visual excitation of ... Full text Link to item Cite

Activation of transducin guanosine triphosphatase by two proteins of the RGS family.

Journal Article Biochemistry · June 24, 1997 RGS proteins (regulators of G protein signaling) constitute a newly appreciated group of negative regulators of G protein signaling. Several members of this group stimulate the guanosine triphosphatase (GTPase) activity of various G protein alpha-subunits, ... Full text Link to item Cite

Activation of transducin GTPase by two proteins from the RGS family

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · March 15, 1997 Link to item Cite

cGMP signal termination.

Journal Article Biochem Soc Trans · November 1996 Full text Link to item Cite

Interaction sites of the COOH-terminal region of the gamma subunit of cGMP phosphodiesterase with the GTP-bound alpha subunit of transducin.

Journal Article J Biol Chem · October 25, 1996 In photoreceptor cells, visual transduction occurs through photoexcitation of rhodopsin, GTP activation of the alpha subunit of transducin, and interaction between GTP-bound transducin alpha subunit and the inhibitory gamma subunit of phosphodiesterase. Th ... Full text Link to item Cite

Phosphorylation of non-bleached rhodopsin in intact retinas and living frogs.

Journal Article J Biol Chem · August 16, 1996 The photoresponse in retinal photoreceptors begins when a molecule of rhodopsin is excited by a photon of light. Photoexcited rhodopsin activates an enzymatic cascade including the G-protein transducin and cyclic GMP phosphodiesterase. As a result, cytopla ... Full text Link to item Cite

Interaction sites of the C-terminal region of the 7 subunit of cgmp phosphodiesterase(P7) with the Q subunit of transducin (AT)

Conference FASEB Journal · 1996 In photoreceptor cells, visual transduction occurs through at and P7 interaction. Trp70 has been implicated in PDE activation, at-P7 interaction and GAP activity. We have derivatized P7 with a reversible photoactivatable reagent-I25/-ACTP at Cys68. A light ... Cite

An effector site that stimulates G-protein GTPase in photoreceptors.

Journal Article J Biol Chem · June 16, 1995 Heterotrimeric G-proteins mediate between receptors and effectors, acting as molecular clocks. G-protein interactions with activated receptors catalyze the replacement of GDP bound to the alpha-subunit with GTP. alpha-Subunits then modulate the activity of ... Full text Link to item Cite

What are the mechanisms of photoreceptor adaptation?

Journal Article Behavioral and Brain Sciences · January 1, 1995 This article evaluates each of the reactions known to be involved in visual transduction as a potential site for the regulation of light adaptation. Extensive evidence suggests that calcium acts as a feedback messenger at several different points and recen ... Full text Cite

Regulation of transducin GTPase activity in bovine rod outer segments.

Journal Article J Biol Chem · August 5, 1994 The photoreceptor G-protein, transducin, belongs to the class of heterotrimeric GTP-binding proteins that transfer information from activated seven-span membrane receptors to effector enzymes or ion channels. Like other G-proteins, transducin acts as a mol ... Link to item Cite

Rod outer segment structure influences the apparent kinetic parameters of cyclic GMP phosphodiesterase.

Journal Article J Gen Physiol · June 1994 Cyclic GMP hydrolysis by the phosphodiesterase (PDE) of retinal rod outer segments (ROS) is a key amplification step in phototransduction. Definitive estimates of the turnover number, kcat, and of the Km are crucial to quantifying the amplification contrib ... Full text Link to item Cite

cGMP binding sites on photoreceptor phosphodiesterase: role in feedback regulation of visual transduction.

Journal Article Proc Natl Acad Sci U S A · May 24, 1994 A central step in vertebrate visual transduction is the rapid drop in cGMP levels that causes cGMP-gated ion channels in the photoreceptor cell membrane to close. It has long been a puzzle that the cGMP phosphodiesterase (PDE) whose activation causes this ... Full text Link to item Cite

Two types of mechanosensitive channels in the Escherichia coli cell envelope: solubilization and functional reconstitution.

Journal Article Biophys J · July 1993 Mechanosensitive ion channels (MSCs) which could provide for fast osmoregulatory responses in bacteria, remain unidentified as molecular entities. MSCs from Escherichia coli (strain AW740) were examined using the patch-clamp technique, either (a) in giant ... Full text Link to item Cite

Noncatalytic cGMP-binding sites of amphibian rod cGMP phosphodiesterase control interaction with its inhibitory gamma-subunits. A putative regulatory mechanism of the rod photoresponse.

Journal Article J Biol Chem · December 5, 1992 The cGMP phosphodiesterase (PDE) of retinal rods plays a central role in phototransduction. Illumination leads to its activation by a rod G-protein (Gt, transducin), thus causing a decrease in intracellular cGMP concentration, closure of plasma membrane ca ... Link to item Cite

Regulation of deactivation of photoreceptor G protein by its target enzyme and cGMP.

Journal Article Nature · June 4, 1992 The photoreceptor G protein, transducin, is one of the class of heterotrimeric G proteins that mediates between membrane receptors and intracellular enzymes or ion channels. Light-activated rhodopsin catalyses the exchange of GDP for GTP on multiple transd ... Full text Link to item Cite

cGMP suppresses GTPase activity of a portion of transducin equimolar to phosphodiesterase in frog rod outer segments. Light-induced cGMP decreases as a putative feedback mechanism of the photoresponse.

Journal Article J Biol Chem · October 5, 1991 In rod photoreceptor cells, the light response is triggered by an enzymatic cascade that causes cGMP levels to fall: excited rhodopsin (Rho*)----rod G-protein (transducin, Gt)----cGMP-phosphodiesterase (PDE). This results in the closure of plasma membrane ... Link to item Cite

Transducin GTPase provides for rapid quenching of the cGMP cascade in rod outer segments.

Journal Article FEBS Lett · July 3, 1989 The role of transducin GTPase in rapid cGMP phosphodiesterase quenching was studied by simultaneous registration of GTP hydrolysis and phosphodiesterase activity in the same rod outer segments (ROS) preparation. The results thus obtained allow the conclusi ... Full text Link to item Cite

On the role of transducin GTPase in the quenching of a phosphodiesterase cascade of vision.

Journal Article FEBS Lett · November 16, 1987 The rate of GTP hydrolysis in the active site of transducin and that of the release of the phosphate thus formed have been measured. The former step has been found to be a rate-limiting one. The rate constant for GTP hydrolysis is equal to 0.027 s-1 at 23 ... Full text Link to item Cite

The effect of rhodopsin phosphorylation on the light-dependent activation of phosphodiesterase from bovine rod outer segments.

Journal Article FEBS Lett · February 25, 1985 ATP quenches light-dependent phosphodiesterase (PDE) activation in rod outer segments presumably due to rhodopsin phosphorylation. Here we compared the efficiency of phosphorylated and non-phosphorylated rhodopsins as PDE activators in a reconstituted cell ... Full text Link to item Cite