Activation of GPCRs modulates quantal size in chromaffin cells through Gβγ and PKC

Xiao Ke Chen; Lie Cheng Wang; Yang Zhou; Qian Cai; Murali Prakriya; Kai Lai Duan; Zu Hang Sheng; Christopher Lingle; Zhuan Zhou

doi:10.1038/nn1529

Activation of GPCRs modulates quantal size in chromaffin cells through G_βγ and PKC

Xiao Ke Chen, Lie Cheng Wang, Yang Zhou, Qian Cai, Murali Prakriya, Kai Lai Duan, Zu Hang Sheng, Christopher Lingle, Zhuan Zhou^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

96 Scopus citations

Abstract

Exocytosis proceeds by either full fusion or 'kiss-and-run' between vesicle and plasma membrane. Switching between these two modes permits the cell to regulate the kinetics and amount of secretion. Here we show that ATP receptor activation reduces secretion downstream from cytosolic Ca²⁺ elevation in rat adrenal chromaffin cells. This reduction is mediated by activation of a pertussis toxin-sensitive G_i/o protein, leading to activation of G_βγ subunits, which promote the 'kiss-and-run' mode by reducing the total open time of the fusion pore during a vesicle fusion event. Furthermore, parallel activation of the muscarinic acetylcholine receptor removes the inhibitory effects of ATP on secretion. This is mediated by a G _q pathway through protein kinase C activation. The inhibitory effects of ATP and its reversal by protein kinase C activation are also shared by opioids and somatostatin. Thus, a variety of G protein pathways exist to modulate Ca²⁺-evoked secretion at specific steps in fusion pore formation.

Original language	English (US)
Pages (from-to)	1160-1168
Number of pages	9
Journal	Nature neuroscience
Volume	8
Issue number	9
DOIs	https://doi.org/10.1038/nn1529
State	Published - Sep 2005

Funding

We thank C. He for the Gb1g2 peptide, Y.T. Wang for the dynamin peptides and I. Bruce for reading the manuscript. This work was supported by grants from the National Basic Research Program of China (G2000077800 and 2006CB500800), the National Natural Science Foundation of China (30330210, 303328013 and C010505 to Z.Z.) and the US National Institutes of Health (DK46564 to C.L.).

ASJC Scopus subject areas

General Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nn1529

Cite this

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title = "Activation of GPCRs modulates quantal size in chromaffin cells through Gβγ and PKC",

abstract = "Exocytosis proceeds by either full fusion or 'kiss-and-run' between vesicle and plasma membrane. Switching between these two modes permits the cell to regulate the kinetics and amount of secretion. Here we show that ATP receptor activation reduces secretion downstream from cytosolic Ca2+ elevation in rat adrenal chromaffin cells. This reduction is mediated by activation of a pertussis toxin-sensitive Gi/o protein, leading to activation of Gβγ subunits, which promote the 'kiss-and-run' mode by reducing the total open time of the fusion pore during a vesicle fusion event. Furthermore, parallel activation of the muscarinic acetylcholine receptor removes the inhibitory effects of ATP on secretion. This is mediated by a G q pathway through protein kinase C activation. The inhibitory effects of ATP and its reversal by protein kinase C activation are also shared by opioids and somatostatin. Thus, a variety of G protein pathways exist to modulate Ca2+-evoked secretion at specific steps in fusion pore formation.",

author = "Chen, {Xiao Ke} and Wang, {Lie Cheng} and Yang Zhou and Qian Cai and Murali Prakriya and Duan, {Kai Lai} and Sheng, {Zu Hang} and Christopher Lingle and Zhuan Zhou",

note = "Funding Information: We thank C. He for the Gb1g2 peptide, Y.T. Wang for the dynamin peptides and I. Bruce for reading the manuscript. This work was supported by grants from the National Basic Research Program of China (G2000077800 and 2006CB500800), the National Natural Science Foundation of China (30330210, 303328013 and C010505 to Z.Z.) and the US National Institutes of Health (DK46564 to C.L.).",

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AU - Chen, Xiao Ke

AU - Wang, Lie Cheng

AU - Zhou, Yang

AU - Cai, Qian

AU - Prakriya, Murali

AU - Duan, Kai Lai

AU - Sheng, Zu Hang

AU - Lingle, Christopher

AU - Zhou, Zhuan

N1 - Funding Information: We thank C. He for the Gb1g2 peptide, Y.T. Wang for the dynamin peptides and I. Bruce for reading the manuscript. This work was supported by grants from the National Basic Research Program of China (G2000077800 and 2006CB500800), the National Natural Science Foundation of China (30330210, 303328013 and C010505 to Z.Z.) and the US National Institutes of Health (DK46564 to C.L.).

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N2 - Exocytosis proceeds by either full fusion or 'kiss-and-run' between vesicle and plasma membrane. Switching between these two modes permits the cell to regulate the kinetics and amount of secretion. Here we show that ATP receptor activation reduces secretion downstream from cytosolic Ca2+ elevation in rat adrenal chromaffin cells. This reduction is mediated by activation of a pertussis toxin-sensitive Gi/o protein, leading to activation of Gβγ subunits, which promote the 'kiss-and-run' mode by reducing the total open time of the fusion pore during a vesicle fusion event. Furthermore, parallel activation of the muscarinic acetylcholine receptor removes the inhibitory effects of ATP on secretion. This is mediated by a G q pathway through protein kinase C activation. The inhibitory effects of ATP and its reversal by protein kinase C activation are also shared by opioids and somatostatin. Thus, a variety of G protein pathways exist to modulate Ca2+-evoked secretion at specific steps in fusion pore formation.

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