A diacidic motif determines unconventional secretion of wild-type and ALS-linked mutant SOD1

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• dc.contributor.author Cruz-Garcia, David
• dc.contributor.author Brouwers, Nathalie
• dc.contributor.author Duran, Juan M.
• dc.contributor.author Mora, Gabriel
• dc.contributor.author Curwin, Amy
• dc.contributor.author Malhotra, Vivek
• dc.date.accessioned 2023-12-11T06:48:05Z
• dc.date.available 2023-12-11T06:48:05Z
• dc.date.issued 2017
• dc.description.abstract The nutrient starvation-specific unconventional secretion of Acb1 in Saccharomyces cerevisiae requires ESCRT-I, -II, and -III and Grh1. In this study, we report that another signal sequence lacking cytoplasmic protein, superoxide dismutase 1 (SOD1), and its mutant form linked to amyotrophic lateral sclerosis (ALS), is also secreted by yeast upon nutrient starvation in a Grh1- and ESCRT-I–, -II–, and -III–dependent process. Our analyses reveal that a conserved diacidic motif (Asp-Glu) in these proteins is necessary for their export. Importantly, secretion of wild-type human SOD1 and the ALS-linked mutant in human cells also require the diacidic residues. Altogether, these findings reveal information encoded within the cytoplasmic proteins required for their unconventional secretion and provide a means to unravel the significance of the cytoplasmic versus the secreted form of mutant SOD1 in the pathology of ALS. We also propose how cells, based on a signal-induced change in cytoplasmic physiology, select a small pool of a subset of cytoplasmic proteins for unconventional secretion.
• dc.description.sponsorship We acknowledge support from the Spanish Ministry of Economy and Competitiveness through the program Centro de Excelencia Severo Ochoa 2013–2017 (SEV-2012-0208) and from the Centres de Recerca de Catalunya Program/Generalitat de Catalunya. Vivek Malhotra is an Institució Catalana de Recerca i Estudis Avançats professor at the Center for Genomic Regulation, and the work in his laboratory is funded by grants from the Spanish Ministry of Economy and Competitiveness’s Plan Nacional (BFU2013-44188-P) and Consolider (CSD2009-00016) as well as by the European Research Council (268692). The project has received research funding from the European Union. This paper reflects only the authors’ views. The European Union is not liable for any use that may be made of the information contained therein.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cruz-Garcia D, Brouwers N, Duran JM, Mora G, Curwin AJ, Malhotra V. A diacidic motif determines unconventional secretion of wild-type and ALS-linked mutant SOD1. Journal of Cell Biology. 2017 Sep 4;216(9):2691-700. DOI: 10.1083/jcb.201704056
• dc.identifier.doi http://dx.doi.org/10.1083/jcb.201704056
• dc.identifier.issn 0021-9525
• dc.identifier.uri http://hdl.handle.net/10230/58487
• dc.language.iso eng
• dc.publisher Rockefeller University Press
• dc.relation.ispartof Journal of Cell Biology. 2017 Sep 4;216(9):2691-700
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/268692
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-44188-P
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2009-00016
• dc.rights © 2017 Cruz-Garcia et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/4.0/
• dc.subject.keyword Disease
• dc.subject.keyword Trafficking
• dc.title A diacidic motif determines unconventional secretion of wild-type and ALS-linked mutant SOD1
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion