Cholesterol regulates Syntaxin 6 trafficking at the TGN-endosomal boundaries

Inhibition 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...

Descripción completa

Detalles Bibliográficos
Autores: Reverter Martín, Meritxell, Rentero Alfonso, Carles, García Melero, Ana, Hoque, Monira, Vilà de Muga, Sandra, Álvarez-Guaita, Anna, Conway, James, Wood, Peta, Cairns, Rose, Lykopoulou, Lila, Grinberg Vaisman, Daniel Raúl, Vilageliu i Arqués, Lluïsa, Bosch i Rodríguez, Marta, Heeren, Joerg, Blasi Cabús, Joan, Timpson, Paul, Pol i Sorolla, Albert, Tebar Ramon, Francesc, Murray, Rachael Z., Grewal, Thomas
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/54324
Acceso en línea:https://hdl.handle.net/2445/54324
Access Level:acceso abierto
Palabra clave:Colesterol
Transport biològic
Biologia molecular
Aparell de Golgi
Cholesterol
Biological transport
Molecular biology
Golgi apparatus
Descripción
Sumario:Inhibition 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.

Similares en LA Referencia