Control of plasma membrane lipid homeostasis by the extended synaptotagmins
Acute metabolic changes in plasma membrane (PM) lipids, such as those mediating signalling reactions, are rapidly compensated by homeostatic responses whose molecular basis is poorly understood. Here we show that the extended synaptotagmins (E-Syts), endoplasmic reticulum (ER) proteins that function...
Saved in:
Main Authors: | , , , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2016
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/80526 http://hdl.handle.net/10220/40524 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-80526 |
---|---|
record_format |
dspace |
spelling |
sg-ntu-dr.10356-805262022-02-16T16:29:49Z 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 Lee Kong Chian School of Medicine (LKCMedicine) Calcium signalling Endoplasmic reticulum Lipid signalling Membrane trafficking Acute metabolic changes in plasma membrane (PM) lipids, such as those mediating signalling reactions, are rapidly compensated by homeostatic responses whose molecular basis is poorly understood. Here we show that the extended synaptotagmins (E-Syts), endoplasmic reticulum (ER) proteins that function as PtdIns(4,5)P2- and Ca2+-regulated tethers to the PM, participate in these responses. E-Syts transfer glycerolipids between bilayers in vitro, and this transfer requires Ca2+ and their lipid-harbouring SMP domain. Genome-edited cells lacking E-Syts do not exhibit abnormalities in the major glycerolipids at rest, but exhibit enhanced and sustained accumulation of PM diacylglycerol following PtdIns(4,5)P2 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-Syt-dependent ER–PM tethers in response to stimuli that cleave PtdIns(4,5)P2 and elevate Ca2+ may help reverse accumulation of diacylglycerol in the PM by transferring it to the ER for metabolic recycling. Accepted version 2016-05-11T08:12:02Z 2019-12-06T13:51:30Z 2016-05-11T08:12:02Z 2019-12-06T13:51:30Z 2016 Journal Article Saheki, Y., Bian, X., Schauder, C. M., Sawaki, Y., Surma, M. A., Klose, C., et al. (2016). Control of plasma membrane lipid homeostasis by the extended synaptotagmins. Nature Cell Biology, 18(5), 504-515. 1465-7392 https://hdl.handle.net/10356/80526 http://hdl.handle.net/10220/40524 10.1038/ncb3339 27065097 en Nature Cell Biology © 2016 Macmillan Publishers Ltd. This is the author created version of a work that has been peer reviewed and accepted for publication by Nature Cell Biology, Macmillan Publishers Ltd. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1038/ncb3339]. 54 p. application/pdf |
institution |
Nanyang Technological University |
building |
NTU Library |
continent |
Asia |
country |
Singapore Singapore |
content_provider |
NTU Library |
collection |
DR-NTU |
language |
English |
topic |
Calcium signalling Endoplasmic reticulum Lipid signalling Membrane trafficking |
spellingShingle |
Calcium signalling Endoplasmic reticulum Lipid signalling Membrane trafficking 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 |
description |
Acute metabolic changes in plasma membrane (PM) lipids, such as those mediating signalling reactions, are rapidly compensated by homeostatic responses whose molecular basis is poorly understood. Here we show that the extended synaptotagmins (E-Syts), endoplasmic reticulum (ER) proteins that function as PtdIns(4,5)P2- and Ca2+-regulated tethers to the PM, participate in these responses. E-Syts transfer glycerolipids between bilayers in vitro, and this transfer requires Ca2+ and their lipid-harbouring SMP domain. Genome-edited cells lacking E-Syts do not exhibit abnormalities in the major glycerolipids at rest, but exhibit enhanced and sustained accumulation of PM diacylglycerol following PtdIns(4,5)P2 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-Syt-dependent ER–PM tethers in response to stimuli that cleave PtdIns(4,5)P2 and elevate Ca2+ may help reverse accumulation of diacylglycerol in the PM by transferring it to the ER for metabolic recycling. |
author2 |
Lee Kong Chian School of Medicine (LKCMedicine) |
author_facet |
Lee Kong Chian School of Medicine (LKCMedicine) Saheki, Yasunori Bian, Xin Schauder, Curtis M. Sawaki, Yujin Surma, Michal A. Klose, Christian Pincet, Frederic Reinisch, Karin M. De Camilli, Pietro |
format |
Article |
author |
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 |
title |
Control of plasma membrane lipid homeostasis by the extended synaptotagmins |
title_short |
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_sort |
control of plasma membrane lipid homeostasis by the extended synaptotagmins |
publishDate |
2016 |
url |
https://hdl.handle.net/10356/80526 http://hdl.handle.net/10220/40524 |
_version_ |
1725985679795552256 |