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PMID: 26001273 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport.

eLife ·Vol. 4 ·2015-05-22

Gatta AT, Wong LH, Sere YY, Calderón-Noreña DM, Cockcroft S, Menon AK, Levine TP

Abstract

Sterol traffic between the endoplasmic reticulum (ER) and plasma membrane (PM) is a fundamental cellular process that occurs by a poorly understood non-vesicular mechanism. We identified a novel, evolutionarily diverse family of ER membrane proteins with StART-like lipid transfer domains and studied them in yeast. StART-like domains from Ysp2p and its paralog Lam4p specifically bind sterols, and Ysp2p, Lam4p and their homologs Ysp1p and Sip3p target punctate ER-PM contact sites distinct from those occupied by known ER-PM tethers. The activity of Ysp2p, reflected in amphotericin-sensitivity assays, requires its second StART-like domain to be positioned so that it can reach across ER-PM contacts. Absence of Ysp2p, Ysp1p or Sip3p reduces the rate at which exogenously supplied sterols traffic from the PM to the ER. Our data suggest that these StART-like proteins act in trans to mediate a step in sterol exchange between the PM and ER.

Keywords
S. cerevisiae StART protein VASt domains cell biology cholesterol ergosterol lipid traffic membrane contact sites polyenes
MeSH Terms
Biological Transport/physiology Carrier Proteins/metabolism Cell Membrane/metabolism Computational Biology Endoplasmic Reticulum/metabolism HL-60 Cells Humans Mitochondrial Proteins/metabolism Plasmids/genetics Polymerase Chain Reaction Saccharomyces cerevisiae Proteins/metabolism Sterols/metabolism
Chemicals
Carrier Proteins Mitochondrial Proteins Saccharomyces cerevisiae Proteins Sterols Ysp2 protein, S cerevisiae
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Gatta Alberto T ORCID
Department of Cell Biology, UCL Institute of Ophthalmology, London, United Kingdom.
Wong Louise H
Department of Cell Biology, UCL Institute of Ophthalmology, London, United Kingdom.
Sere Yves Y
Department of Biochemistry, Weill Cornell Medical College, New York, United States.
Calderón-Noreña Diana M
Department of Biochemistry, Weill Cornell Medical College, New York, United States.
Cockcroft Shamshad
Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom.
Menon Anant K ORCID
Department of Biochemistry, Weill Cornell Medical College, New York, United States.
Levine Tim P
Department of Cell Biology, UCL Institute of Ophthalmology, London, United Kingdom.
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Article Info
Journal
eLife
Abbr.
Elife
ISSN
2050-084X
DOI
10.7554/eLife.07253
Published
2015-05-22
Epub
2015-00-22
Language
English
Region
England
NLM ID
101579614
PMCID
PMC4463742
Subset
IM
Grants
Biotechnology and Biological Sciences Research Council · BB/M011801/1 · United Kingdom
Medical Research Council · MR/J006580/1 · United Kingdom
External Links
PubMed source DOI: 10.7554/eLife.07253 PMC Full Text View journal details
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