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Control of plasma membrane lipid homeostasis by the extended synaptotagmins

Acute metabolic changes of plasma membrane (PM) lipids, such as those mediating signaling reactions, are rapidly compensated by homeostatic responses whose molecular basis is poorly understood. Here we show that the Extended-Synaptotagmins (E-Syts), ER proteins which function as PI(4,5)P(2) and Ca(2...

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Autores principales: Saheki, Yasunori, Bian, Xin, Schauder, Curtis M., Sawaki, Yujin, Surma, Michal A., Klose, Christian, Pincet, Frederic, Reinisch, Karin M., De Camilli, Pietro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848133/
https://www.ncbi.nlm.nih.gov/pubmed/27065097
http://dx.doi.org/10.1038/ncb3339
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author Saheki, Yasunori
Bian, Xin
Schauder, Curtis M.
Sawaki, Yujin
Surma, Michal A.
Klose, Christian
Pincet, Frederic
Reinisch, Karin M.
De Camilli, Pietro
author_facet Saheki, Yasunori
Bian, Xin
Schauder, Curtis M.
Sawaki, Yujin
Surma, Michal A.
Klose, Christian
Pincet, Frederic
Reinisch, Karin M.
De Camilli, Pietro
author_sort Saheki, Yasunori
collection PubMed
description Acute metabolic changes of plasma membrane (PM) lipids, such as those mediating signaling reactions, are rapidly compensated by homeostatic responses whose molecular basis is poorly understood. Here we show that the Extended-Synaptotagmins (E-Syts), ER proteins which function as PI(4,5)P(2) and Ca(2+)-regulated tethers to the PM, participate in these responses. E-Syts transfer glycerolipids between bilayers in vitro and such transfer requires Ca(2+) and their SMP domain, a lipid-harboring module. Genome edited cells lacking E-Syts do not exhibit abnormalities in the major glycerolipids at rest, but display enhanced and sustained accumulation of PM diacylglycerol (DAG) upon PI(4,5)P(2) hydrolysis by PLC activation, which can be rescued by expression of E-Syt1, but not by mutant E-Syt1 lacking the SMP domain. The formation of E-Syts-dependent ER-PM tethers in response to stimuli that cleave PI(4,5)P(2) and elevate Ca(2+) may help reverse accumulation of DAG in the PM by transferring it to the ER for metabolic recycling.
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spelling pubmed-48481332016-10-11 Control of plasma membrane lipid homeostasis by the extended synaptotagmins Saheki, Yasunori Bian, Xin Schauder, Curtis M. Sawaki, Yujin Surma, Michal A. Klose, Christian Pincet, Frederic Reinisch, Karin M. De Camilli, Pietro Nat Cell Biol Article Acute metabolic changes of plasma membrane (PM) lipids, such as those mediating signaling reactions, are rapidly compensated by homeostatic responses whose molecular basis is poorly understood. Here we show that the Extended-Synaptotagmins (E-Syts), ER proteins which function as PI(4,5)P(2) and Ca(2+)-regulated tethers to the PM, participate in these responses. E-Syts transfer glycerolipids between bilayers in vitro and such transfer requires Ca(2+) and their SMP domain, a lipid-harboring module. Genome edited cells lacking E-Syts do not exhibit abnormalities in the major glycerolipids at rest, but display enhanced and sustained accumulation of PM diacylglycerol (DAG) upon PI(4,5)P(2) hydrolysis by PLC activation, which can be rescued by expression of E-Syt1, but not by mutant E-Syt1 lacking the SMP domain. The formation of E-Syts-dependent ER-PM tethers in response to stimuli that cleave PI(4,5)P(2) and elevate Ca(2+) may help reverse accumulation of DAG in the PM by transferring it to the ER for metabolic recycling. 2016-04-11 2016-05 /pmc/articles/PMC4848133/ /pubmed/27065097 http://dx.doi.org/10.1038/ncb3339 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Saheki, Yasunori
Bian, Xin
Schauder, Curtis M.
Sawaki, Yujin
Surma, Michal A.
Klose, Christian
Pincet, Frederic
Reinisch, Karin M.
De Camilli, Pietro
Control of plasma membrane lipid homeostasis by the extended synaptotagmins
title Control of plasma membrane lipid homeostasis by the extended synaptotagmins
title_full Control of plasma membrane lipid homeostasis by the extended synaptotagmins
title_fullStr Control of plasma membrane lipid homeostasis by the extended synaptotagmins
title_full_unstemmed Control of plasma membrane lipid homeostasis by the extended synaptotagmins
title_short Control of plasma membrane lipid homeostasis by the extended synaptotagmins
title_sort control of plasma membrane lipid homeostasis by the extended synaptotagmins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848133/
https://www.ncbi.nlm.nih.gov/pubmed/27065097
http://dx.doi.org/10.1038/ncb3339
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