Scholars@Duke
Huanghe Yang

Huanghe Yang

Associate Professor of Biochemistry
Biochemistry
huanghe.yang@duke.edu
Box 3711,DUMC, Durham, NC 27710
213 Nanaline H Duke, Box 3711, DUMC, Durham, NC 27710

Selected Publications

TMEM16 and OSCA/TMEM63 proteins share a conserved potential to permeate ions and phospholipids

Journal Article eLife · November 4, 2024 The calcium-activated TMEM16 proteins and the mechanosensitive/osmolarity-activated OSCA/TMEM63 proteins belong to the Transmembrane Channel/Scramblase (TCS) superfamily. Within the superfamily, OSCA/TMEM63 proteins, as well as TMEM16A and TMEM16B, ... Full text Cite

Platelet and red cell responses to three North American pit vipers.

Journal Article Toxicon · August 28, 2024 We investigated the hemotoxic effects of three North American pit vipers in healthy human donor blood. Using experiments focusing on platelet and red blood cell activity, we found differential effects of these venoms on these cellular components. Platelet ... Full text Link to item Cite

Redox-dependent Cd2+ inhibition of BK-type Ca2+-activated K+ channels.

Journal Article Biophys J · July 16, 2024 Large-conductance Ca2+-activated K+ channels (BK channels) are formed by Slo1 subunits as a homotetramer. Besides Ca2+, other divalent cations, such as Cd2+, also activate BK channels when applied intracellularly by shifting the conductance-voltage relatio ... Full text Link to item Cite

TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling.

Journal Article J Cell Sci · July 15, 2024 TMEM16F (also known as ANO6), a Ca2+-activated lipid scramblase (CaPLSase) that dynamically disrupts lipid asymmetry, plays a crucial role in various physiological and pathological processes, such as blood coagulation, neurodegeneration, cell-cell fusion a ... Full text Link to item Cite

Attenuating midline thalamus bursting to mitigate absence epilepsy.

Journal Article Proc Natl Acad Sci U S A · July 9, 2024 Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-funct ... Full text Link to item Cite

Niclosamide potentiates TMEM16A and induces vasoconstriction.

Journal Article J Gen Physiol · July 1, 2024 The TMEM16A calcium-activated chloride channel is a promising therapeutic target for various diseases. Niclosamide, an anthelmintic medication, has been considered a TMEM16A inhibitor for treating asthma and chronic obstructive pulmonary disease (COPD) but ... Full text Link to item Cite

Osmosensor-mediated control of Ca2+ spiking in pollen germination.

Journal Article Nature · May 2024 Higher plants survive terrestrial water deficiency and fluctuation by arresting cellular activities (dehydration) and resuscitating processes (rehydration). However, how plants monitor water availability during rehydration is unknown. Although increases in ... Full text Link to item Cite

Trophoblast organoids with physiological polarity model placental structure and function.

Journal Article J Cell Sci · March 1, 2024 Human trophoblast organoids (TOs) are a three-dimensional ex vivo culture model that can be used to study various aspects of placental development, physiology and pathology. However, standard culturing of TOs does not recapitulate the cellular orientation ... Full text Link to item Cite

Deciphering and disrupting PIEZO1-TMEM16F interplay in hereditary xerocytosis.

Journal Article Blood · January 25, 2024 Cell-surface exposure of phosphatidylserine (PS) is essential for phagocytic clearance and blood clotting. Although a calcium-activated phospholipid scramblase (CaPLSase) has long been proposed to mediate PS exposure in red blood cells (RBCs), its identity ... Full text Link to item Cite

Quantification of Trophoblast Syncytialization by Fluorescent Membrane Labeling.

Journal Article Methods Mol Biol · 2024 Trophoblast fusion or syncytialization is a fundamental yet poorly understood process during placental development. Primary cultured cytotrophoblasts and human choriocarcinoma cell lines are commonly used to study trophoblast fusion mechanisms in vitro. Qu ... Full text Link to item Cite

PIEZO1-TMEM16F Interplay in Hereditary Xerocytosis

Conference Blood · November 2, 2023 Cell surface exposure of phosphatidylserine (PS), an anionic phospholipid that is usually confined to the inner leaflet of the plasma membrane, triggers a plethora of cellular responses. PS exposure in RBCs contributes ... Full text Cite

Transducing Force into Procoagulation: PIEZO1-TMEM16F Functional Coupling in Blood Lining Cells

Conference Blood · November 2, 2023 Thrombosis is a major global disease burden that accounts for 1 in 4 deaths worldwide. Hypertension and preeclampsia greatly increase thrombotic risks by imposing high blood pressure and abnormal hemodynamic shear stres ... Full text Cite

Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion.

Journal Article Elife · June 7, 2022 TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated syncytialization, however, how TMEM16F is activated during cell fusion is unclear. Here, using troph ... Full text Open Access Link to item Cite

Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia.

Journal Article Proc Natl Acad Sci U S A · March 22, 2022 A growing number of gain-of-function (GOF) BK channelopathies have been identified in patients with epilepsy and movement disorders. Nevertheless, the underlying pathophysiology and corresponding therapeutics remain obscure. Here, we utilized a knock-in mo ... Full text Link to item Cite

Epithelia-Sensory Neuron Cross Talk Underlies Cholestatic Itch Induced by Lysophosphatidylcholine.

Journal Article Gastroenterology · July 2021 BACKGROUND & AIMS: Limited understanding of pruritus mechanisms in cholestatic liver diseases hinders development of antipruritic treatments. Previous studies implicated lysophosphatidic acid (LPA) as a potential mediator of cholestatic pruritus. METHODS: ... Full text Link to item Cite

Molecular underpinning of intracellular pH regulation on TMEM16F.

Journal Article J Gen Physiol · February 1, 2021 TMEM16F, a dual-function phospholipid scramblase and ion channel, is important in blood coagulation, skeleton development, HIV infection, and cell fusion. Despite advances in understanding its structure and activation mechanism, how TMEM16F is regulated by ... Full text Link to item Cite

Gating and Regulatory Mechanisms of TMEM16 Ion Channels and Scramblases.

Journal Article Frontiers in physiology · January 2021 The transmembrane protein 16 (TMEM16) family consists of Ca2+-activated ion channels and Ca2+-activated phospholipid scramblases (CaPLSases) that passively flip-flop phospholipids between the two leaflets of the membrane bilayer. Owin ... Full text Open Access Cite

Structure-Function of TMEM16 Ion Channels and Lipid Scramblases.

Journal Article Adv Exp Med Biol · 2021 The TMEM16 protein family comprises two novel classes of structurally conserved but functionally distinct membrane transporters that function as Ca2+-dependent Cl- channels (CaCCs) or dual functional Ca2+-dependent ion channels and phospholipid scramblases ... Full text Link to item Cite

An Additional Ca2+ Binding Site Allosterically Controls TMEM16A Activation.

Journal Article Cell Rep · December 29, 2020 Calcium (Ca2+) is the primary stimulus for transmembrane protein 16 (TMEM16) Ca2+-activated chloride channels and phospholipid scramblases, which regulate important physiological processes ranging from smooth muscle contraction to blood coagulation and tum ... Full text Link to item Cite

Identification of BBOX1 as a Therapeutic Target in Triple-Negative Breast Cancer.

Journal Article Cancer Discov · November 2020 Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease. Because of its heterogeneity and lack of hormone receptors or HER2 expression, targeted therapy is limited. Here, by performing a functional siRNA screening for 2-OG-dependent ... Full text Link to item Cite

A Gain-of-Function Mutation in KCNMA1 Causes Dystonia Spells Controlled With Stimulant Therapy.

Journal Article Mov Disord · October 2020 BACKGROUND: The mutations of KCNMA1 BK-type K+ channel have been identified in patients with various movement disorders. The underlying pathophysiology and corresponding therapeutics are lacking. OBJECTIVES: To report our clinical and biophysical character ... Full text Link to item Cite

Evidence that polyphenols do not inhibit the phospholipid scramblase TMEM16F.

Journal Article J Biol Chem · August 28, 2020 TMEM16 Ca2+-activated phospholipid scramblases (CaPLSases) mediate rapid transmembrane phospholipid flip-flop and as such play essential roles in various physiological and pathological processes such as blood coagulation, skeletal development, viral infect ... Full text Link to item Cite

TMEM16F phospholipid scramblase mediates trophoblast fusion and placental development.

Journal Article Sci Adv · May 2020 Cell-cell fusion or syncytialization is fundamental to the reproduction, development, and homeostasis of multicellular organisms. In addition to various cell type-specific fusogenic proteins, cell surface externalization of phosphatidylserine (PS), a unive ... Full text Link to item Cite

Molecular basis of PIP2-dependent regulation of the Ca2+-activated chloride channel TMEM16A.

Journal Article Nat Commun · August 21, 2019 The calcium-activated chloride channel (CaCC) TMEM16A plays crucial roles in regulating neuronal excitability, smooth muscle contraction, fluid secretion and gut motility. While opening of TMEM16A requires binding of intracellular Ca2+, prolonged Ca2+-depe ... Full text Link to item Cite

An inner activation gate controls TMEM16F phospholipid scrambling.

Journal Article Nat Commun · April 23, 2019 Transmembrane protein 16F (TMEM16F) is an enigmatic Ca2+-activated phospholipid scramblase (CaPLSase) that passively transports phospholipids down their chemical gradients and mediates blood coagulation, bone development and viral infection. Despite recent ... Full text Link to item Cite

Drosophila Subdued is a moonlighting transmembrane protein 16 (TMEM16) that transports ions and phospholipids.

Journal Article J Biol Chem · March 22, 2019 Transmembrane protein 16 (TMEM16) family members play numerous important physiological roles, ranging from controlling membrane excitability and secretion to mediating blood coagulation and viral infection. These diverse functions are largely due to their ... Full text Link to item Cite

Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel.

Journal Article Science · March 1, 2019 Transient receptor potential melastatin member 8 (TRPM8) is a calcium ion (Ca2+)-permeable cation channel that serves as the primary cold and menthol sensor in humans. Activation of TRPM8 by cooling compounds relies on allosteric actions of agonist and mem ... Full text Link to item Cite

A simple and robust fluorescent labeling method to quantify trophoblast fusion.

Journal Article Placenta · February 2019 Trophoblast fusion into syncytiotrophoblasts is a specialized yet enigmatic cellular process, which is essential for placental development and function. To facilitate mechanistic understanding of this critical process, here we re-purposed a widely used flu ... Full text Link to item Cite

TMEM16F phospholipid scramblase mediates trophoblast fusion and placental development

Journal Article · 2019 Cell-cell fusion or syncytialization is fundamental to the reproduction, development and homeostasis of multicellular organisms. In addition to various cell-type specific fusogenic proteins, cell surface externalization of phosphatidylserine (PS), a univer ... Full text Cite

Conformational plasticity in the selectivity filter of the TRPV2 ion channel.

Journal Article Nat Struct Mol Biol · May 2018 Transient receptor potential vanilloid (TRPV) channels are activated by ligands and heat and are involved in various physiological processes. In contrast to the architecturally related voltage-gated cation channels, TRPV1 and TRPV2 subtypes possess another ... Full text Link to item Cite

Threading the biophysics of mammalian Slo1 channels onto structures of an invertebrate Slo1 channel.

Journal Article J Gen Physiol · November 6, 2017 For those interested in the machinery of ion channel gating, the Ca2+ and voltage-activated BK K+ channel provides a compelling topic for investigation, by virtue of its dual allosteric regulation by both voltage and intracellular Ca2+ and because its larg ... Full text Link to item Cite

Inferior Olivary TMEM16B Mediates Cerebellar Motor Learning.

Journal Article Neuron · August 30, 2017 Ca2+-activated ion channels shape membrane excitability and Ca2+ dynamics in response to cytoplasmic Ca2+ elevation. Compared to the Ca2+-activated K+ channels, known as BK and SK channels, the physiological importance of Ca2+-activated Cl- channels (CaCCs ... Full text Link to item Cite

TMEM16 Membrane Proteins in Health and Disease

Chapter · July 29, 2016 The TransMEMbrane protein 16 (TMEM16) family has received much attention since the discovery of TMEM16A as the long sought-after calcium-activated chloride channels (CaCCs) in 2008. In mammals the TMEM16 family comprises 10 members, which are widely expres ... Full text Cite

EAG2 potassium channel with evolutionarily conserved function as a brain tumor target.

Journal Article Nat Neurosci · September 2015 Over 20% of the drugs for treating human diseases target ion channels, but no cancer drug approved by the US Food and Drug Administration (FDA) is intended to target an ion channel. We found that the EAG2 (Ether-a-go-go 2) potassium channel has an evolutio ... Full text Link to item Cite

BK channels: multiple sensors, one activation gate.

Journal Article Front Physiol · 2015 Ion transport across cell membranes is essential to cell communication and signaling. Passive ion transport is mediated by ion channels, membrane proteins that create ion conducting pores across cell membrane to allow ion flux down electrochemical gradient ... Full text Link to item Cite

BK channels

Chapter · January 1, 2015 Large conductance, voltage, and Ca2+-activated K+ channels are known as BK or MaxiK channels to denote the large single channel conductance of 100-300 pS (Figure 17.1). BK channel currents were rst discovered in the early 1980s when the newly invented patc ... Full text Cite

A charged residue in S4 regulates coupling among the activation gate, voltage, and Ca2+ sensors in BK channels.

Journal Article J Neurosci · September 10, 2014 Coupling between the activation gate and sensors of physiological stimuli during ion channel activation is an important, but not well-understood, molecular process. One difficulty in studying sensor-gate coupling is to distinguish whether a structural pert ... Full text Link to item Cite

A comprehensive search for calcium binding sites critical for TMEM16A calcium-activated chloride channel activity

Journal Article eLife · June 30, 2014 TMEM16A forms calcium-activated chloride channels (CaCCs) that regulate physiological processes such as the secretions of airway epithelia and exocrine glands, the contraction of smooth muscles, and the excitability of neurons. Notwithstanding intense inte ... Full text Cite

A comprehensive search for calcium binding sites critical for TMEM16A calcium-activated chloride channel activity.

Journal Article Elife · June 30, 2014 TMEM16A forms calcium-activated chloride channels (CaCCs) that regulate physiological processes such as the secretions of airway epithelia and exocrine glands, the contraction of smooth muscles, and the excitability of neurons. Notwithstanding intense inte ... Full text Link to item Cite

Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia.

Journal Article Nat Med · June 2014 Cardiomyocyte T tubules are important for regulating ion flux. Bridging integrator 1 (BIN1) is a T-tubule protein associated with calcium channel trafficking that is downregulated in failing hearts. Here we find that cardiac T tubules normally contain dens ... Full text Link to item Cite

The interface between membrane-spanning and cytosolic domains in Ca²+-dependent K+ channels is involved in β subunit modulation of gating.

Journal Article J Neurosci · July 3, 2013 Large-conductance, voltage-, and Ca²⁺-dependent K⁺ (BK) channels are broadly expressed in various tissues to modulate neuronal activity, smooth muscle contraction, and secretion. BK channel activation depends on the interactions among the voltage sensing d ... Full text Link to item Cite

Interaction between residues in the Mg2+-binding site regulates BK channel activation.

Journal Article J Gen Physiol · February 2013 As a unique member of the voltage-gated potassium channel family, a large conductance, voltage- and Ca(2+)-activated K(+) (BK) channel has a large cytosolic domain that serves as the Ca(2+) sensor, in addition to a membrane-spanning domain that contains th ... Full text Link to item Cite

Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction.

Journal Article Proc Natl Acad Sci U S A · October 2, 2012 Mucous cell hyperplasia and airway smooth muscle (ASM) hyperresponsiveness are hallmark features of inflammatory airway diseases, including asthma. Here, we show that the recently identified calcium-activated chloride channel (CaCC) TMEM16A is expressed in ... Full text Link to item Cite

TMEM16F forms a Ca2+-activated cation channel required for lipid scrambling in platelets during blood coagulation.

Journal Article Cell · September 28, 2012 Collapse of membrane lipid asymmetry is a hallmark of blood coagulation. TMEM16F of the TMEM16 family that includes TMEM16A/B Ca(2+)-activated Cl(-) channels (CaCCs) is linked to Scott syndrome with deficient Ca(2+)-dependent lipid scrambling. We generated ... Full text Link to item Cite

Ca2+-activated Cl- channels at a glance.

Journal Article J Cell Sci · March 15, 2012 Full text Link to item Cite

An epilepsy/dyskinesia-associated mutation enhances BK channel activation by potentiating Ca2+ sensing.

Journal Article Neuron · June 24, 2010 Ca(2+)-activated BK channels modulate neuronal activities, including spike frequency adaptation and synaptic transmission. Previous studies found that Ca(2+)-binding sites and the activation gate are spatially separated in the channel protein, but the mech ... Full text Link to item Cite

Molecular mechanisms of BK channel activation.

Journal Article Cell Mol Life Sci · March 2009 Large conductance, Ca(2+)-activated potassium (BK) channels are widely expressed throughout the animal kingdom and play important roles in many physiological processes, such as muscle contraction, neural transmission and hearing. These physiological roles ... Full text Link to item Cite

Activation of Slo1 BK channels by Mg2+ coordinated between the voltage sensor and RCK1 domains.

Journal Article Nat Struct Mol Biol · November 2008 The voltage-sensor domain (VSD) and the ligand sensor (cytoplasmic domain) of BK channels synergistically control channel activities, thereby integrating electrical and chemical signals for cell function. Studies show that intracellular Mg2+ mediates the i ... Full text Link to item Cite

Subunit-specific effect of the voltage sensor domain on Ca2+ sensitivity of BK channels.

Journal Article Biophys J · June 2008 Large conductance Ca(2+)- and voltage-activated K(+) (BK) channels, composed of pore-forming alpha-subunits and auxiliary beta-subunits, play important roles in diverse physiological processes. The differences in BK channel phenotypes are primarily due to ... Full text Link to item Cite

Mg2+ mediates interaction between the voltage sensor and cytosolic domain to activate BK channels.

Journal Article Proc Natl Acad Sci U S A · November 13, 2007 The voltage-sensor domain (VSD) of voltage-dependent ion channels and enzymes is critical for cellular responses to membrane potential. The VSD can also be regulated by interaction with intracellular proteins and ligands, but how this occurs is poorly unde ... Full text Link to item Cite

Tuning magnesium sensitivity of BK channels by mutations.

Journal Article Biophys J · October 15, 2006 Intracellular Mg(2+) at physiological concentrations activates mSlo1 BK channels by binding to a metal-binding site in the cytosolic domain. Previous studies suggest that residues E374, Q397, and E399 are important in Mg(2+) binding. In the present study, ... Full text Link to item Cite

Effects of multiple metal binding sites on calcium and magnesium-dependent activation of BK channels.

Journal Article J Gen Physiol · January 2006 BK channels are activated by physiological concentrations of intracellular Ca2+ and Mg2+ in a variety of cells. Previous studies have identified two sites important for high-affinity Ca2+ sensing between [Ca2+]i of 0.1-100 microM and a site important for M ... Full text Link to item Cite

Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder.

Journal Article Nat Genet · July 2005 The large conductance calcium-sensitive potassium (BK) channel is widely expressed in many organs and tissues, but its in vivo physiological functions have not been fully defined. Here we report a genetic locus associated with a human syndrome of coexisten ... Full text Link to item Cite

The Decomposition of NO in Microwave Discharge

Journal Article Kao Teng Hsueh Hsiao Hua Heush Hsueh Pao/ Chemical Journal of Chinese Universities · April 1, 2002 The decomposition of NO in a continuous microwave discharge was investigated. When (NO, He) mixture was used as the reactant, almost all NO can be converted to N2. In(NO, O2, He) system, the conversion of NO was nearly 80%, and the selectivity of N2 was 80 ... Cite

Direct decomposition of NO by microwave heating over Fe/NaZSM-5

Journal Article Applied Catalysis B: Environmental · February 8, 2002 Catalytic decomposition of NO was studied over Fe/NaZSM-5 catalyst. Novel results were observed with the microwave heating mode. The conversion of NO to N2 increased remarkably with the increasing of Fe loading. The effects of a series of reaction paramete ... Full text Cite

The decomposition of NO in microwave discharge

Journal Article CHEMICAL JOURNAL OF CHINESE UNIVERSITIES-CHINESE · 2002 Cite

Effect of Sr substitution on catalytic activity of La1-xSrxMnO3 (0≤x≤0.8) perovskite-type oxides for catalytic decomposition of hydrogen peroxide

Journal Article Reaction Kinetics and Catalysis Letters · December 1, 2001 La1-XSrXMnO3 (0≤x<0.8) perovskite-type oxides were synthesized by the combined EDTA-citrate complexing method and their catalytic activity for the decomposition of hydrogen peroxide was investigated. Hydrogen peroxide decomposition was observed as a first- ... Full text Cite

Perovskite Type Oxides: A Novel Type of Catalysts Suitable for Hydrogen Peroxide Decomposition

Conference European Space Agency, (Special Publication) ESA SP · December 1, 2001 La1-xSrxMnO3 (0 ≤ x ≤ 0.8) Perovskite-type oxide powders were synthesized by sol-gel method and their catalytic activity for the H2O2 decomposition was investigated. H2O2 decomposition was observed as first-order reaction on these catalysts. With the incre ... Cite

Removal of NO by microwave discharge with the addition of CH4

Journal Article Chemistry Letters · January 1, 2001 Removal of NO by a continuous microwave discharge at atmospheric pressure with the addition of CH4 is reported. The conversion of NO to N2 is approximately 80%, and the energy efficiency is up to 0.55 g-NO/kWh. The effects of CH4 addition and three dischar ... Full text Cite

Manganese-lead mixed oxide catalysts for decomposition of hydrogen peroxide

Journal Article Chinese Journal of Catalysis · November 1, 2000 Alumina-supported manganese-lead oxide catalysts were prepared, and their activity for the decomposition of hydrogen peroxide was assessed by the refractometric method. Lead oxide as an additive promotes remarkably the activity of manganese oxide and the c ... Cite