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Regulating quantal size of neurotransmitter release through a GPCR voltage sensor

by Lin, Zhaohan , Zhu, Feipeng , Yin, Lili , Huang, Rong , Sun, Xiaoxuan , Zhou, Zhuan , Zhang, Quanfeng , Wu, Qihui , Liu, Bing , Liu, Bin , Li, Yinglin , Younus, Muhammad , Jiang, Xiaohan

in Action potential / Action Potentials / Animals / Biological Sciences / Calcium channels (voltage-gated) / Calcium influx / Calcium ions / Catecholamine / Catecholamines / Catecholamines - metabolism / Cell activation / Chromaffin cells / Chromaffin Cells - physiology / Contractility / Depolarization / Electric potential / Exocytosis / Female / G protein-coupled receptors / HEK293 Cells / Heterotrimeric GTP-Binding Proteins - metabolism / Humans / Ions / Male / Membrane potential / Membrane vesicles / Membranes / Mice, Knockout / Myocytes / Nervous system / Neuroscience / Neurotransmitter release / Neurotransmitters / Primary Cell Culture / Proteins / Rats, Sprague-Dawley / Receptors / Receptors, Purinergic P2Y12 - metabolism / Secretory Vesicles - physiology / Signal Transduction / Vesicle fusion / Voltage

2020

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Regulating quantal size of neurotransmitter release through a GPCR voltage sensor

by Lin, Zhaohan , Zhu, Feipeng , Yin, Lili , Huang, Rong , Sun, Xiaoxuan , Zhou, Zhuan , Zhang, Quanfeng , Wu, Qihui , Liu, Bing , Liu, Bin , Li, Yinglin , Younus, Muhammad , Jiang, Xiaohan

2020

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Regulating quantal size of neurotransmitter release through a GPCR voltage sensor

by Lin, Zhaohan , Zhu, Feipeng , Yin, Lili , Huang, Rong , Sun, Xiaoxuan , Zhou, Zhuan , Zhang, Quanfeng , Wu, Qihui , Liu, Bing , Liu, Bin , Li, Yinglin , Younus, Muhammad , Jiang, Xiaohan

2020

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Journal Article

Regulating quantal size of neurotransmitter release through a GPCR voltage sensor

Lin, Zhaohan,

Zhu, Feipeng,

Yin, Lili,

Huang, Rong,

Sun, Xiaoxuan,

Zhou, Zhuan,

Zhang, Quanfeng,

Wu, Qihui,

Liu, Bing,

Liu, Bin,

Li, Yinglin,

Younus, Muhammad,

Jiang, Xiaohan

2020

Overview

Current models emphasize thatmembrane voltage (Vm) depolarization-induced Ca2+ influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Giβγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca2+, Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS. The Vm regulation of QS was through ATP-activated GPCR-P2Y12 receptors. D76 and D127 in P2Y12 were the voltage-sensing sites. Finally, we revealed the relevance of the Vm dependence of QS for tuning autoinhibition and target cell functions. Together, membrane voltage per se increases the quantal size of dense-core vesicle release of catecholamine via Vm → P2Y12(D76/D127) → Giβγ → QS → myocyte contractility, offering a universal Vm-GPCR signaling pathway for its functions in the nervous system and other systems containing GPCRs.

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Publisher

National Academy of Sciences

Subject

Action potential

/ Action Potentials

/ Animals

/ Biological Sciences

/ Calcium channels (voltage-gated)

/ Calcium influx

/ Calcium ions