van Galen, JosseCampelo, FelixMartínez-Alonso, EmmaScarpa, MargheritaMartínez-Menárguez, José ÁngelMalhotra, Vivek2025-01-202025-01-202014van 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.2014050090021-9525http://hdl.handle.net/10230/69191Do 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.application/pdfeng© 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/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.1083/jcb.201405009info:eu-repo/semantics/openAccess