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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/54324
Cholesterol regulates Syntaxin 6 trafficking at the TGN-endosomal boundaries
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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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REVERTER MARTÍN, Meritxell, et al. Cholesterol regulates Syntaxin 6 trafficking at the TGN-endosomal boundaries. Cell Reports. 2014. Vol. 7, num. 3, pags. 883-897. ISSN 2211-1247. [consulted: 6 of June of 2026]. Available at: https://hdl.handle.net/2445/54324