Cholesterol regulates Syntaxin 6 trafficking at the TGN-endosomal boundaries
| Autor: | Reverter Martín, Meritxell, Rentero Alfonso, Carles, Garcia-Melero, Ana, Hoque, Monira, Vilà de Muga, Sandra, Alvarez-Guaita, Anna, Conway, James, Wood, Peta, Cairns, Rose, Lykopoulou, Lila, Grinberg Vaisman, Daniel Raúl, Vilageliu i Arqués, Lluïsa, Bosch, Marta (Bosch Rodríguez), Heeren, Joerg, Blasi Cabús, Joan, Timpson, Paul, Pol i Sorolla, Albert, Tebar Ramon, Francesc, Murray, Rachael Z., Grewal, Thomas |
|---|---|
| Přispěvatelé: | Universitat de Barcelona |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|