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.
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.
Impact and interest:
Citation counts are sourced monthly from and citation databases.
These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.
Citations counts from theindexing service can be viewed at the linked Google Scholar™ search.
Full-text downloads displays the total number of times this work’s files (e.g., a PDF) have been downloaded from QUT ePrints as well as the number of downloads in the previous 365 days. The count includes downloads for all files if a work has more than one.
|Item Type:||Journal Article|
|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:||04 Apr 2017 07:49|
Repository Staff Only: item control page