SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells

Abstract Insulin secretion from pancreatic ß cells is a multistep process that requires the coordination of exocytotic proteins that integrate diverse signals. These include signals derived from metabolic control of post-translational SUMOylation and depolarization-induced rises in intracellular Ca2...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mourad Ferdaoussi, Jianyang Fu, Xiaoqing Dai, Jocelyn E. Manning Fox, Kunimasa Suzuki, Nancy Smith, Gregory Plummer, Patrick E. MacDonald
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/051a727042634a409608aa2b2820abb6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:051a727042634a409608aa2b2820abb6
record_format	dspace
spelling	oai:doaj.org-article:051a727042634a409608aa2b2820abb62021-12-02T15:05:16ZSUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells10.1038/s41598-017-00344-z2045-2322https://doaj.org/article/051a727042634a409608aa2b2820abb62017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00344-zhttps://doaj.org/toc/2045-2322Abstract Insulin secretion from pancreatic ß cells is a multistep process that requires the coordination of exocytotic proteins that integrate diverse signals. These include signals derived from metabolic control of post-translational SUMOylation and depolarization-induced rises in intracellular Ca2+. Here we show that tomosyn, which suppresses insulin exocytosis by binding syntaxin1A, does so in a manner which requires its SUMOylation. Glucose-dependent de-SUMOylation of tomosyn1 at K298 releases syntaxin1A and controls the amplification of exocytosis in concert with a recently-identified tomosyn1-interacting partner; the Ca2+-binding protein secretagogin, which dissociates from tomosyn1 in response to Ca2+-raising stimuli and is required for insulin granule trafficking and exocytosis downstream of Ca2+ influx. Together our results suggest that tomosyn acts as a key signaling hub in insulin secretion by integrating signals mediated by metabolism-dependent de-SUMOylation and electrically-induced entry of Ca2+ to regulate the availability of exocytotic proteins required for the amplification of insulin secretion.Mourad FerdaoussiJianyang FuXiaoqing DaiJocelyn E. Manning FoxKunimasa SuzukiNancy SmithGregory PlummerPatrick E. MacDonaldNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mourad Ferdaoussi Jianyang Fu Xiaoqing Dai Jocelyn E. Manning Fox Kunimasa Suzuki Nancy Smith Gregory Plummer Patrick E. MacDonald SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells
description	Abstract Insulin secretion from pancreatic ß cells is a multistep process that requires the coordination of exocytotic proteins that integrate diverse signals. These include signals derived from metabolic control of post-translational SUMOylation and depolarization-induced rises in intracellular Ca2+. Here we show that tomosyn, which suppresses insulin exocytosis by binding syntaxin1A, does so in a manner which requires its SUMOylation. Glucose-dependent de-SUMOylation of tomosyn1 at K298 releases syntaxin1A and controls the amplification of exocytosis in concert with a recently-identified tomosyn1-interacting partner; the Ca2+-binding protein secretagogin, which dissociates from tomosyn1 in response to Ca2+-raising stimuli and is required for insulin granule trafficking and exocytosis downstream of Ca2+ influx. Together our results suggest that tomosyn acts as a key signaling hub in insulin secretion by integrating signals mediated by metabolism-dependent de-SUMOylation and electrically-induced entry of Ca2+ to regulate the availability of exocytotic proteins required for the amplification of insulin secretion.
format	article
author	Mourad Ferdaoussi Jianyang Fu Xiaoqing Dai Jocelyn E. Manning Fox Kunimasa Suzuki Nancy Smith Gregory Plummer Patrick E. MacDonald
author_facet	Mourad Ferdaoussi Jianyang Fu Xiaoqing Dai Jocelyn E. Manning Fox Kunimasa Suzuki Nancy Smith Gregory Plummer Patrick E. MacDonald
author_sort	Mourad Ferdaoussi
title	SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells
title_short	SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells
title_full	SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells
title_fullStr	SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells
title_full_unstemmed	SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells
title_sort	sumoylation and calcium control syntaxin-1a and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/051a727042634a409608aa2b2820abb6
work_keys_str_mv	AT mouradferdaoussi sumoylationandcalciumcontrolsyntaxin1aandsecretagoginsequestrationbytomosyntoregulateinsulinexocytosisinhumanßcells AT jianyangfu sumoylationandcalciumcontrolsyntaxin1aandsecretagoginsequestrationbytomosyntoregulateinsulinexocytosisinhumanßcells AT xiaoqingdai sumoylationandcalciumcontrolsyntaxin1aandsecretagoginsequestrationbytomosyntoregulateinsulinexocytosisinhumanßcells AT jocelynemanningfox sumoylationandcalciumcontrolsyntaxin1aandsecretagoginsequestrationbytomosyntoregulateinsulinexocytosisinhumanßcells AT kunimasasuzuki sumoylationandcalciumcontrolsyntaxin1aandsecretagoginsequestrationbytomosyntoregulateinsulinexocytosisinhumanßcells AT nancysmith sumoylationandcalciumcontrolsyntaxin1aandsecretagoginsequestrationbytomosyntoregulateinsulinexocytosisinhumanßcells AT gregoryplummer sumoylationandcalciumcontrolsyntaxin1aandsecretagoginsequestrationbytomosyntoregulateinsulinexocytosisinhumanßcells AT patrickemacdonald sumoylationandcalciumcontrolsyntaxin1aandsecretagoginsequestrationbytomosyntoregulateinsulinexocytosisinhumanßcells
_version_	1718388871974092800

SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells

Ejemplares similares