Sphingomyelin homeostasis is required to form functional enzymatic domains at the trans-Golgi network

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  • dc.contributor.author van Galen, Josse
  • dc.contributor.author Campelo, Felix
  • dc.contributor.author Martínez-Alonso, Emma
  • dc.contributor.author Scarpa, Margherita
  • dc.contributor.author Martínez-Menárguez, José Ángel
  • dc.contributor.author Malhotra, Vivek
  • dc.date.accessioned 2025-01-20T07:43:20Z
  • dc.date.available 2025-01-20T07:43:20Z
  • dc.date.issued 2014
  • dc.description.abstract Do lipids such as sphingomyelin (SM) that are known to assemble into specific membrane domains play a role in the organization and function of transmembrane proteins? In this paper, we show that disruption of SM homeostasis at the trans-Golgi network (TGN) by treatment of HeLa cells with d-ceramide-C6, which was converted together with phosphatidylcholine to short-chain SM and diacylglycerol by SM synthase, led to the segregation of Golgi-resident proteins from each other. We found that TGN46, which cycles between the TGN and the plasma membrane, was not sialylated by a sialyltransferase at the TGN and that this enzyme and its substrate TGN46 could not physically interact with each other. Our results suggest that SM organizes transmembrane proteins into functional enzymatic domains at the TGN.en
  • dc.description.sponsorship We thank the members of the Malhotra laboratory for valuable discussions. We thank Dr. S. Ponnambalam for the kind gift of the TGN46-GFP construct. We thank Dr. K. Saito for cloning ST-FKBP-RFP. All confocal imaging was performed in the Center for Genomic Regulation Advanced Light Microscopy Unit. We acknowledge support from the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa 2013–2017” (SEV-2012-0208). F. Campelo was partially funded by a Juan de la Cierva fellowship. V. 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 Plan Nacional (BFU2008-00414), Consolider (CSD2009-00016), Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) Grups de Recerca Emergents (SGR2009-1488; AGAUR-Catalan Government), and the European Research Council (268692). The project has received research funding from the European Union. This paper reflects only the author’s views. The Union is not liable for any use that may be made of the information contained therein. The authors declare no competing financial interests.en
  • dc.format.mimetype application/pdf
  • dc.identifier.citation van Galen J, Campelo F, Martínez-Alonso E, Scarpa M, Martínez-Menárguez JÁ, Malhotra V. Sphingomyelin homeostasis is required to form functional enzymatic domains at the trans-Golgi network. J Cell Biol. 2014 Sep 1;206(5):609-18. DOI: 10.1083/jcb.201405009
  • dc.identifier.doi http://dx.doi.org/10.1083/jcb.201405009
  • dc.identifier.issn 0021-9525
  • dc.identifier.uri http://hdl.handle.net/10230/69191
  • dc.language.iso eng
  • dc.publisher Rockefeller University Press
  • dc.relation.ispartof Journal of Cell Biology. 2014 Sep 1;206(5):609-18
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/268692
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SEV-2012-0208
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2008-00414
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2009-00016
  • dc.rights © 2014 van Galen 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/
  • dc.title Sphingomyelin homeostasis is required to form functional enzymatic domains at the trans-Golgi networken
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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