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PMID: 27065097 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Control of plasma membrane lipid homeostasis by the extended synaptotagmins.

Nature cell biology ·Vol. 18 ·No. 5 ·2016-00-00 ·Pages 504-15

Saheki Y, Bian X, Schauder CM, Sawaki Y, Surma MA, Klose C, Pincet F, Reinisch KM, De Camilli P

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.

MeSH Terms
Biological Transport CRISPR-Cas Systems Calcium/metabolism Carrier Proteins/metabolism Cell Membrane/metabolism Cytosol/metabolism Diglycerides/metabolism Endoplasmic Reticulum/metabolism Enzyme Activation Gene Knockout Techniques HeLa Cells Homeostasis Humans Membrane Lipids/metabolism Synaptotagmins/metabolism Transcription Activator-Like Effector Nucleases/metabolism Type C Phospholipases/metabolism
Chemicals
Carrier Proteins Diglycerides Membrane Lipids lipid transfer protein Synaptotagmins Transcription Activator-Like Effector Nucleases Type C Phospholipases Calcium
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Saheki Yasunori
Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Bian Xin
Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Schauder Curtis M
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Sawaki Yujin
Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Surma Michal A
Lipotype GmbH, Am Tatzberg 47-49, 01307 Dresden, Germany.
Klose Christian
Lipotype GmbH, Am Tatzberg 47-49, 01307 Dresden, Germany.
Pincet Frederic
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | 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.
Reinisch Karin M
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
De Camilli Pietro
Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA. | Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb3339
Published
2016-00-00
Epub
2016-00-11
Pages
504-15
Language
English
Region
England
NLM ID
100890575
PMCID
PMC4848133
Subset
IM
Grants
NCI NIH HHS · P01 CA046128 · United States
NIDA NIH HHS · P30 DA018343 · United States
NIDDK NIH HHS · R01 DK082700 · United States
NIDDK NIH HHS · P30 DK045735 · United States
NCRR NIH HHS · P41 RR000592 · United States
NINDS NIH HHS · R37 NS036251 · United States
NIGMS NIH HHS · R01 GM080616 · United States
Corrections
CommentIn
PMID: 27117329
External Links
PubMed source DOI: 10.1038/ncb3339 PMC Full Text View journal details
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