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Akiyoshi Uezu

Assistant Research Professor of Cell Biology
Cell Biology
303 Research Drive, 471 Sands, Durham, NC 27710

Selected Publications


Identification of New Ciliary Signaling Pathways in the Brain and Insights into Neurological Disorders.

Journal Article J Neurosci · August 13, 2025 Primary cilia are conserved sensory hubs essential for signaling transduction and embryonic development. Ciliary dysfunction causes a variety of developmental syndromes with neurological features and cognitive impairment whose basis mostly remains unknown. ... Full text Link to item Cite

The Nedd4L ubiquitin ligase is activated by FCHO2-generated membrane curvature.

Journal Article EMBO J · December 2024 The C2-WW-HECT domain ubiquitin ligase Nedd4L regulates membrane sorting during endocytosis through the ubiquitination of cargo molecules such as the epithelial sodium channel (ENaC). Nedd4L is catalytically autoinhibited by an intramolecular interaction b ... Full text Link to item Cite

Map7D2 and Map7D1 facilitate microtubule stabilization through distinct mechanisms in neuronal cells.

Journal Article Life Sci Alliance · August 2022 Microtubule (MT) dynamics are modulated through the coordinated action of various MT-associated proteins (MAPs). However, the regulatory mechanisms underlying MT dynamics remain unclear. We show that the MAP7 family protein Map7D2 stabilizes MTs to control ... Full text Link to item Cite

Chemico-genetic discovery of astrocytic control of inhibition in vivo.

Journal Article Nature · December 2020 Perisynaptic astrocytic processes are an integral part of central nervous system synapses1,2; however, the molecular mechanisms that govern astrocyte-synapse adhesions and how astrocyte contacts control synapse formation and function are largely unknown. H ... Full text Link to item Cite

Essential role for InSyn1 in dystroglycan complex integrity and cognitive behaviors in mice.

Journal Article Elife · December 12, 2019 Human mutations in the dystroglycan complex (DGC) result in not only muscular dystrophy but also cognitive impairments. However, the molecular architecture critical for the synaptic organization of the DGC in neurons remains elusive. Here, we report Inhibi ... Full text Link to item Cite

Plug-and-Play Protein Modification Using Homology-Independent Universal Genome Engineering.

Journal Article Neuron · August 21, 2019 Analysis of endogenous protein localization, function, and dynamics is fundamental to the study of all cells, including the diversity of cell types in the brain. However, current approaches are often low throughput and resource intensive. Here, we describe ... Full text Link to item Cite

In vivo proximity proteomics of nascent synapses reveals a novel regulator of cytoskeleton-mediated synaptic maturation.

Journal Article Nat Commun · January 23, 2019 Excitatory synapse formation during development involves the complex orchestration of both structural and functional alterations at the postsynapse. However, the molecular mechanisms that underlie excitatory synaptogenesis are only partially resolved, in p ... Full text Link to item Cite

Map7/7D1 and Dvl form a feedback loop that facilitates microtubule remodeling and Wnt5a signaling.

Journal Article EMBO Rep · July 2018 The Wnt signaling pathway can be grouped into two classes, the β-catenin-dependent and β-catenin-independent pathways. Wnt5a signaling through a β-catenin-independent pathway promotes microtubule (MT) remodeling during cell-substrate adhesion, cell migrati ... Full text Link to item Cite

Identification of an elaborate complex mediating postsynaptic inhibition.

Journal Article Science · September 9, 2016 Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization. The composition of the inhibitory postsynapse and the mechanistic basis of its regulation, however, remain poorly understood. We used an in vivo chemico-genetic proximity- ... Full text Link to item Cite

Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine.

Journal Article Nat Neurosci · June 2015 Psychiatric and neurodevelopmental disorders may arise from anomalies in long-range neuronal connectivity downstream of pathologies in dendritic spines. However, the mechanisms that may link spine pathology to circuit abnormalities relevant to atypical beh ... Full text Link to item Cite

Astrocytes refine cortical connectivity at dendritic spines.

Journal Article Elife · December 17, 2014 During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. ... Full text Open Access Link to item Cite

Modified SH2 domain to phototrap and identify phosphotyrosine proteins from subcellular sites within cells.

Journal Article Proc Natl Acad Sci U S A · October 23, 2012 Spatial regulation of tyrosine phosphorylation is important for many aspects of cell biology. However, phosphotyrosine accounts for less than 1% of all phosphorylated substrates, and it is typically a very transient event in vivo. These factors complicate ... Full text Link to item Cite

Peptide array X-linking (PAX): a new peptide-protein identification approach.

Journal Article PLoS One · 2012 Many protein interaction domains bind short peptides based on canonical sequence consensus motifs. Here we report the development of a peptide array-based proteomics tool to identify proteins directly interacting with ligand peptides from cell lysates. Arr ... Full text Link to item Cite

SH3 domain-based phototrapping in living cells reveals Rho family GAP signaling complexes.

Journal Article Sci Signal · November 29, 2011 Rho family GAPs [guanosine triphosphatase (GTPase) activating proteins] negatively regulate Rho family GTPase activity and therefore modulate signaling events that control cytoskeletal dynamics. The spatial distribution of these GAPs and their specificity ... Full text Link to item Cite

Characterization of the EFC/F-BAR domain protein, FCHO2.

Journal Article Genes Cells · August 2011 We have previously shown that SGIP1α is an endocytic protein specifically expressed in neural tissues. SGIP1α has a lipid-binding domain called the MP domain, which shows no significant homology to any other domains. In this study, we characterized FCHO2, ... Full text Link to item Cite

Mass spectrometric analysis of microtubule co-sedimented proteins from rat brain.

Journal Article Genes Cells · April 2008 Microtubules (MTs) play crucial roles in a variety of cell functions, such as mitosis, vesicle transport and cell motility. MTs also compose specialized structures, such as centrosomes, spindles and cilia. However, molecular mechanisms of these MT-based fu ... Full text Link to item Cite

Identification and characterization of the novel centrosomal protein centlein.

Journal Article Biochem Biophys Res Commun · February 22, 2008 Centrosomes function as the major microtubule (MT)-organizing center. They are composed of a pair of centrioles which are surrounded by the pericentriolar material. Here, we describe the molecular characterization of a novel protein, named centlein (centro ... Full text Link to item Cite

SGIP1alpha is an endocytic protein that directly interacts with phospholipids and Eps15.

Journal Article J Biol Chem · September 7, 2007 SGIP1 has been shown to be an endophilin-interacting protein that regulates energy balance, but its function is not fully understood. Here, we identified its splicing variant of SGIP1 and named it SGIP1alpha. SGIP1alpha bound to phosphatidylserine and phos ... Full text Link to item Cite

Cloning, characterization and expression of two alternatively splicing isoforms of Ca2+/calmodulin-dependent protein kinase I gamma in the rat brain.

Journal Article J Neurochem · June 2003 Ca2+/calmodulin-dependent protein kinase I (CaMKI), originally identified as a protein kinase phosphorylating synapsin I, has been shown to constitute a family of closely related isoforms (alpha, beta and gamma). Here, we have isolated and determined the c ... Full text Link to item Cite

Activation of Ca2+/calmodulin-dependent protein kinase I in cultured rat hippocampal neurons.

Journal Article J Neurochem · August 2002 We have focused on activation mechanisms of calcium/calmodulin-dependent protein kinase (CaM) kinase I in the hippocampal neurons and compared them with that of CaM kinase IV. Increased activation of CaM kinase I occurred by stimulation with glutamate and ... Full text Link to item Cite