Reverter Martín, MeritxellRentero Alfonso, CarlesGarcía Melero, AnaHoque, MoniraVilà de Muga, SandraÁlvarez-Guaita, AnnaConway, JamesWood, PetaCairns, RoseLykopoulou, LilaGrinberg Vaisman, Daniel RaúlVilageliu i Arqués, LluïsaBosch i Rodríguez, MartaHeeren, JoergBlasi Cabús, JoanTimpson, PaulPol i Sorolla, AlbertTebar Ramon, FrancescMurray, Rachael Z.Grewal, Thomas2014-05-212014-05-212014-05-082211-1247https://hdl.handle.net/2445/54324Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN). Here, using Chinese hamster ovary (CHO) Niemann-Pick type C1 (NPC1) mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6) accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs). This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion.15 p.application/pdfengcc-by (c) Reverter Martín, Meritxell et al., 2014http://creativecommons.org/licenses/by/3.0/esColesterolTransport biològicBiologia molecularAparell de GolgiCholesterolBiological transportMolecular biologyGolgi apparatusinfo:eu-repo/semantics/article6360702014-05-21info:eu-repo/semantics/openAccess24746815