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Cholesterol regulates Syntaxin 6 trafficking at trans-Golgi network 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 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 alphaVbeta3 and alpha5beta1 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.

Type Journal
ISBN 2211-1247 (Electronic)
Authors Reverter, M. ; Rentero, C. ; Garcia-Melero, A. ; Hoque, M. ; Vila de Muga, S. ; Alvarez-Guaita, A. ; Conway, J. R. ; Wood, P. ; Cairns, R. ; Lykopoulou, L. ; Grinberg, D. ; Vilageliu, L. ; Bosch, M. ; Heeren, J. ; Blasi, J. ; Timpson, P. ; Pol, A. ; Tebar, F. ; Murray, R. Z. ; Grewal, T. ; Enrich, C.;
Publisher Name Cell Reports
Published Date 2014-01-01
Published Volume 7
Published Issue 3
Published Pages 883-97
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version