Cholesterol regulates Syntaxin 6 trafficking at trans-Golgi network endosomal boundaries.

Reverter, Meritxell, Rentero, Carles, Garcia-Melero, Ana, Hoque, Monira, Vilà de Muga, Sandra, Álvarez-Guaita, Anna, Conway, James R.W., Wood, Peta, Cairns, Rose, Lykopoulou, Lilia, Grinberg, Daniel, Vilageliu, Lluïsa, Bosch, Marta, Heeren, Joerg, Blasi, Juan, Timpson, Paul, Pol, Albert, Tebar, Francesc, Murray, Rachael Z., Grewal, Thomas, & Enrich, Carlos (2014) Cholesterol regulates Syntaxin 6 trafficking at trans-Golgi network endosomal boundaries. Cell Reports, 7(3), pp. 883-897.

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Abstract

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.

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ID Code: 73670
Item Type: Journal Article
Refereed: Yes
DOI: 10.1016/j.celrep.2014.03.043
ISSN: 2211-1247
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 10 Jul 2014 00:13
Last Modified: 11 Jul 2014 06:34

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