Yeshi Wang

Chinese Institute for Brain Research

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Zhuan Zhou

Peking University

Lianghong Zheng

Chinese Institute for Brain Research

Changhe Wang

Xi'an Jiaotong University

Qihui Wu

Chinese Institute for Brain Research

Wei Xiong

Chinese Institute for Brain Research

Meiqin Hu

Zhejiang University

Hui Zheng

First Affiliated Hospital of Hunan University of Traditional Chinese Medicine

Xi Wu

Shanghai Zhangjiang Laboratory

Zuying Chai

Johns Hopkins Medicine

Tao Liu

Peking University

Cooperative Institutions

Peking University

Center for Life Sciences

Chinese Institute for Brain Research

Chinese Academy of Sciences

Shanghai Jiao Tong University

Institute of Molecular Medicine

Zhejiang University

Chinese Academy of Medical Sciences & Peking Union Medical College

McGovern Institute for Brain Research

Capital Medical University

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Action Potential Modulates Ca2+-Dependent and Ca2+-Independent Secretion in a Sensory Neuron

Biophysical Journal (2009)

Hui Zheng Juan Fan Wei Xiong Chen Zhang Xiaobing Wang

Dorsal root ganglion

Postsynaptic Current

10.1016/j.bpj.2008.11.037

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Citations (17)

Extracellular Ca2+ Directly Inhibits Exocytosis in Neurons

Biophysical Journal (2011)

Wei Xiong Tao Liu Yeshi Wang Xaiowei Chen Lei Sun

10.1016/j.bpj.2010.12.1232

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Citations (0)

Intracellular TRPA1 mediates Ca2+ release from lysosomes in dorsal root ganglion neurons

The Journal of Cell Biology (2016)

Shujiang Shang Feipeng Zhu Bin Liu Zuying Chai Qihui Wu

Transient receptor potential A1 (TRPA1) is a nonselective cation channel implicated in thermosensation and inflammatory pain. In this study, we show that TRPA1 (activated by allyl isothiocyanate, acrolein, and 4-hydroxynonenal) elevates the intracellular Ca2+ concentration ([Ca2+]i) in dorsal root ganglion (DRG) neurons in the presence and absence of extracellular Ca2+. Pharmacological and immunocytochemical analyses revealed the presence of TRPA1 channels both on the plasma membrane and in endolysosomes. Confocal line-scan imaging demonstrated Ca2+ signals elicited from individual endolysosomes (“lysosome Ca2+ sparks”) by TRPA1 activation. In physiological solutions, the TRPA1-mediated endolysosomal Ca2+ release contributed to ∼40% of the overall [Ca2+]i rise and directly triggered vesicle exocytosis and calcitonin gene-related peptide release, which greatly enhanced the excitability of DRG neurons. Thus, in addition to working via Ca2+ influx, TRPA1 channels trigger vesicle release in sensory neurons by releasing Ca2+ from lysosome-like organelles.

Dorsal root ganglion

10.1083/jcb.201603081

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Citations (54)

Ligand- and voltage-gated Ca ²⁺ channels differentially regulate the mode of vesicular neuropeptide release in mammalian sensory neurons

Science Signaling (2017)

Yeshi Wang Qihui Wu Meiqin Hu Bin Liu Zuying Chai

Neuropeptides released from dorsal root ganglion (DRG) neurons play essential roles in the neurotransmission of sensory inputs, including those underlying nociception and pathological pain. Neuropeptides are released from intracellular vesicles through two modes: a partial release mode called "kiss-and-run" (KAR) and a full release mode called "full fusion-like" (FFL). Using total internal reflection fluorescence (TIRF) microscopy, we traced the release of pH-sensitive green fluorescent protein-tagged neuropeptide Y (pHluorin-NPY) from individual dense-core vesicles in the soma and axon of single DRG neurons after Ca2+ influx through either voltage-gated Ca2+ channels (VGCCs) or ligand-gated transient receptor potential vanilloid 1 (TRPV1) channels. We found that Ca2+ influx through VGCCs stimulated FFL and a greater single release of neuropeptides. In contrast, Ca2+ influx through TRPV1 channels stimulated KAR and a pulsed but prolonged release of neuropeptides that was partially mediated by Dynamin 1, which limits fusion pore expansion. Suppressing the Ca2+ gradient to an extent similar to that seen after TRPV1 activation abolished the VGCC preference for FFL. The findings suggest that by generating a steeper Ca2+ gradient, VGCCs promote a more robust fusion pore opening that facilitates FFL. Thus, KAR and FFL release modes are differentially regulated by the two principal types of Ca2+-permeable channels in DRG neurons.

Dorsal root ganglion

10.1126/scisignal.aal1683

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Citations (40)

Synaptotagmin‐11 inhibits clathrin‐mediated and bulk endocytosis

EMBO Reports (2015)

Changhe Wang Yeshi Wang Meiqin Hu Zuying Chai Qihui Wu

10.15252/embr.201540689

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Citations (51)

Two distinct vesicle pools for depolarization‐induced exocytosis in somata of dorsal root ganglion neurons

The Journal of Physiology (2011)

Tao Liu Shujiang Shang Bin Liu Changhe Wang Yeshi Wang

The somata of dorsal root ganglion (DRG) neurons release neurotransmitters and neuropeptides. In addition to the conventional Ca2+-dependent secretion (CDS), Ca2+-independent but voltage-dependent secretion (CIVDS) also occurs in the somata of DRG neurons. Electrical stimulation induces both CDS and CIVDS, which differ in size and are coupled with different types of endocytosis contributed by CIVDS and CDS, respectively. However, it is unclear whether they use a common vesicle pool, so we investigated the relationship between the vesicle pools of CDS and CIVDS. Membrane capacitance recording and photolysis of a caged-Ca2+ compound showed that, in low external Ca2+ solutions, the depolarization-induced exocytosis contained two (fast and slow) phases, which were contributed by CIVDS and CDS, respectively. Depletion of the CDS readily releasable pool using photolysis did not affect the CIVDS. When the CIVDS and CDS vesicle pools were depleted by electrical stimulation, the pools had different sizes. Their kinetics of exocytosis-coupled endocytosis were also different. Thus, CIVDS and CDS used different vesicle pools in DRG neurons.

Dorsal root ganglion

Kiss-and-run fusion

10.1113/jphysiol.2011.208777

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Citations (16)

Real-time endocytosis imaging as a rapid assay of ligand-GPCR binding in single cells

AJP Cell Physiology (2013)

Lianghong Zheng Changhe Wang Shujiang Shang Xiaoyu Zhang Yeshi Wang

Most G protein-coupled receptors (GPCRs) do not generate membrane currents in response to ligand-receptor binding (LRB). Here, we describe a novel technique using endocytosis as a bioassay that can detect activation of a GPCR in a way analogous to patch-clamp recording of an ion channel in a living cell. The confocal imaging technique, termed FM endocytosis imaging (FEI), can record ligand-GPCR binding with high temporal (second) and spatial (micrometer) resolution. LRB leads to internalization of an endocytic vesicle, which can be labeled by a styryl FM dye and visualized as a fluorescent spot. Distinct from the green fluorescence protein-labeling method, FEI can detect LRB endocytosis mediated by essentially any receptors (GPCRs or receptors of tyrosine kinase) in a native cell/cell line. Three modified versions of FEI permit promising applications in functional GPCR studies and drug screening in living cells: 1) LRB can be recorded in “real time” (time scale of seconds); 2) internalized vesicles mediated by different GPCRs can be discriminated by different colors; and 3) a high throughput method can screen ligands of a specific GPCR.

Internalization

Live cell imaging

10.1152/ajpcell.00335.2012

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Citations (1)

Extracellular Ca2+ per se inhibits quantal size of catecholamine release in adrenal slice chromaffin cells

Cell Calcium (2014)

Shujiang Shang Changhe Wang Bin Liu Qihui Wu Quanfeng Zhang

Extracellular vesicles

Chromaffin cell

Calcium in biology

Vesicle fusion