The Sec1/Munc18 protein Vps45 regulates cellular levels of its SNARE binding partners Tlg2 and Snc2 in Saccharomyces cerevisiae

Hong, W., Shanks, S.G., Carpp, L.N., Struthers, M.S., McCann, R.K. and Bryant, N.J. (2012) The Sec1/Munc18 protein Vps45 regulates cellular levels of its SNARE binding partners Tlg2 and Snc2 in Saccharomyces cerevisiae. PLoS ONE, 7(11), e49628. (doi: 10.1371/journal.pone.0049628) (PMID:23166732) (PMCID:PMC3498219)

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Abstract

Intracellular membrane trafficking pathways must be tightly regulated to ensure proper functioning of all eukaryotic cells. Central to membrane trafficking is the formation of specific SNARE (soluble N-ethylmeleimide-sensitive factor attachment protein receptor) complexes between proteins on opposing lipid bilayers. The Sec1/Munc18 (SM) family of proteins play an essential role in SNARE-mediated membrane fusion, and like the SNAREs are conserved through evolution from yeast to humans. The SM protein Vps45 is required for the formation of yeast endosomal SNARE complexes and is thus essential for traffic through the endosomal system. Here we report that, in addition to its role in regulating SNARE complex assembly, Vps45 regulates cellular levels of its SNARE binding partners: the syntaxin Tlg2 and the v-SNARE Snc2: Cells lacking Vps45 have reduced cellular levels of Tlg2 and Snc2; and elevation of Vps45 levels results in concomitant increases in the levels of both Tlg2 and Snc2. As well as regulating traffic through the endosomal system, the Snc v-SNAREs are also required for exocytosis. Unlike most vps mutants, cells lacking Vps45 display multiple growth phenotypes. Here we report that these can be reversed by selectively restoring Snc2 levels in vps45 mutant cells. Our data indicate that as well as functioning as part of the machinery that controls SNARE complex assembly, Vps45 also plays a key role in determining the levels of its cognate SNARE proteins; another key factor in regulation of membrane traffic.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bryant, Dr Nia and Shanks, Dr Scott
Authors: Hong, W., Shanks, S.G., Carpp, L.N., Struthers, M.S., McCann, R.K., and Bryant, N.J.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
Published Online:14 November 2012
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in PLoS ONE 7(11):e49628
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
537651Regulation of membrane fusion by a novel Sec1/Munc18-associated proteinMichael BlattBiotechnology and Biological Sciences Research Council (BBSRC)BB/H024867/1RI MOLECULAR CELL & SYSTEMS BIOLOGY