ESCRT-III drives the final stages of CUPS maturation for unconventional protein secretion

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  • dc.contributor.author Curwin, Amyca
  • dc.contributor.author Brouwers, Nathalieca
  • dc.contributor.author Alonso Y Adell, Manuelca
  • dc.contributor.author Teis, Davidca
  • dc.contributor.author Turacchio, Gabrieleca
  • dc.contributor.author Parashuraman, Seetharamanca
  • dc.contributor.author Ronchi, Paoloca
  • dc.contributor.author Malhotra, Vivekca
  • dc.date.accessioned 2017-01-16T12:00:19Z
  • dc.date.available 2017-01-16T12:00:19Z
  • dc.date.issued 2016ca
  • dc.description.abstract The unconventional secretory pathway exports proteins that bypass the endoplasmic reticulum. In Saccharomyces cerevisiae, conditions that trigger Acb1 secretion via this pathway generate a Grh1 containing compartment composed of vesicles and tubules surrounded by a cup-shaped membrane and collectively called CUPS. Here we report a quantitative assay for Acb1 secretion that reveals requirements for ESCRT-I, -II, and -III but, surprisingly, without the involvement of the Vps4 AAA-ATPase. The major ESCRT-III subunit Snf7 localizes transiently to CUPS and this was accelerated in vps4Δ cells, correlating with increased Acb1 secretion. Microscopic analysis suggests that, instead of forming intraluminal vesicles with the help of Vps4, ESCRT-III/Snf7 promotes direct engulfment of preexisting Grh1 containing vesicles and tubules into a saccule to generate a mature Acb1 containing compartment. This novel multivesicular / multilamellar compartment, we suggest represents the stable secretory form of CUPS that is competent for the release of Acb1 to cells exterior.
  • dc.description.sponsorship We acknowledge support from the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208. V. Malhotra is an Institució Catalana de Recerca i Estudis Avançats (ICREA) professor at the Center for Genomic Regulation and the work in his laboratory is funded by grants from Plan Nacional (BFU2008-00414), Consolider (CSD2009-00016), and European Research Council (268692). Work was in the Teis lab funded by HFSP-CDA-00001/2010-C, Austrian Science Fund (FWF), Y444-B12, MCBO (W1101-B18), SFB021 (F21).
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Curwin A, Brouwers N, Alonso Y Adell M, Teis D, Turacchio G, Parashuraman S, Ronchi P, Malhotra V. ESCRT-III drives the final stages of CUPS maturation for unconventional protein secretion. eLife. 2016; 5: e16299. DOI: 10.7554/eLife.16299ca
  • dc.identifier.doi http://dx.doi.org/10.7554/eLife.16299
  • dc.identifier.issn 2050-084Xca
  • dc.identifier.uri http://hdl.handle.net/10230/27904
  • dc.language.iso engca
  • dc.publisher eLifeca
  • dc.relation.ispartof eLife. 2016; 5: e16299
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/268692ca
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SEV2012-0208
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2008-00414
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2009-00016
  • dc.rights © Copyright Curwin et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword CUPS
  • dc.subject.keyword ESCRTs
  • dc.subject.keyword S. cerevisiae
  • dc.subject.keyword Unconventional secretion
  • dc.title ESCRT-III drives the final stages of CUPS maturation for unconventional protein secretionca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca