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Nat Cell Biol. 2016 May;18(5):504-15. doi: 10.1038/ncb3339. Epub 2016 Apr 11.

Control of plasma membrane lipid homeostasis by the extended synaptotagmins.

Saheki Y1,2,3,4,5, Bian X1,2,3,4,5, Schauder CM2, Sawaki Y1,2,3,4,5, Surma MA6, Klose C6, Pincet F2,7, Reinisch KM2, De Camilli P1,2,3,4,5.

Author information

1
Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
2
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
3
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
4
Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
5
Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
6
Lipotype GmbH, Am Tatzberg 47-49, 01307 Dresden, Germany.
7
Laboratoire de Physique Statistique, Ecole Normale Supérieure de Paris, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique, UMR 8550, 24 rue Lhomond, 75005 Paris, France.

Abstract

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 Ca(2+)-regulated tethers to the PM, participate in these responses. E-Syts transfer glycerolipids between bilayers in vitro, and this transfer requires Ca(2+) 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 Ca(2+) may help reverse accumulation of diacylglycerol in the PM by transferring it to the ER for metabolic recycling.

PMID:
27065097
PMCID:
PMC4848133
DOI:
10.1038/ncb3339
[Indexed for MEDLINE]
Free PMC Article

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