BAG3 regulates formation of the SNARE complex and insulin secretion

Cell Death & Disease
V IorioM C Turco

Abstract

Insulin release in response to glucose stimulation requires exocytosis of insulin-containing granules. Glucose stimulation of beta cells leads to focal adhesion kinase (FAK) phosphorylation, which acts on the Rho family proteins (Rho, Rac and Cdc42) that direct F-actin remodeling. This process requires docking and fusion of secretory vesicles to the release sites at the plasma membrane and is a complex mechanism that is mediated by SNAREs. This transiently disrupts the F-actin barrier and allows the redistribution of the insulin-containing granules to more peripheral regions of the β cell, hence facilitating insulin secretion. In this manuscript, we show for the first time that BAG3 plays an important role in this process. We show that BAG3 downregulation results in increased insulin secretion in response to glucose stimulation and in disruption of the F-actin network. Moreover, we show that BAG3 binds to SNAP-25 and syntaxin-1, two components of the t-SNARE complex preventing the interaction between SNAP-25 and syntaxin-1. Upon glucose stimulation BAG3 is phosphorylated by FAK and dissociates from SNAP-25 allowing the formation of the SNARE complex, destabilization of the F-actin network and insulin release.

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Citations

May 11, 2016·Trends in Pharmacological Sciences·Christian Behl
Sep 24, 2016·Experimental & Molecular Medicine·Hye Yun KimJeong-Hwa Lee
Jul 12, 2017·Journal of Cellular Physiology·Giuseppe DerosaMaria C Turco
May 24, 2019·Journal of Cellular and Molecular Medicine·Ye YuanHua-Qin Wang
Jul 7, 2017·Frontiers in Molecular Neuroscience·Elisabeth Stürner, Christian Behl
Aug 20, 2015·American Journal of Physiology. Endocrinology and Metabolism·Caroline Arous, Philippe A Halban
May 4, 2020·Biochimica Et Biophysica Acta. General Subjects·Liberato MarzulloMargot De Marco
May 6, 2021·Metabolites·Nicholas NorrisMelkam Alamerew Kebede
Sep 8, 2021·The Journal of Clinical Investigation·Shane P SimonettAlan D Attie

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Methods Mentioned

BETA
co-immunoprecipitation
immunoprecipitation
ELISA
transfection

Software Mentioned

ImageJ
Adobe Photoshop
Adobe Illustrator

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