Cholesterol regulates Syntaxin 6 trafficking at trans-Golgi network endosomal boundaries.
Por:
Reverter M, Rentero C, Garcia-Melero A, Hoque M, Vilà de Muga S, Alvarez-Guaita A, Conway JR, Wood P, Cairns R, Lykopoulou L, Grinberg-Vaisman DR, Vilageliu L, Bosch M, Heeren J, Blasi J, Timpson P, Pol A, Tebar F, Murray RZ, Grewal T and Enrich C
Publicada:
8 may 2014
Ahead of Print:
17 abr 2014
Categoría:
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Resumen:
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 aVß3 and a5ß1 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.
Filiaciones:
Reverter M:
Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
Rentero C:
Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
Garcia-Melero A:
Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
Hoque M:
Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia
Vilà de Muga S:
Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
Alvarez-Guaita A:
Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
Conway JR:
Garvan Institute of Medical Research and Kinghorn Cancer Centre, Cancer Research Program, St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
Wood P:
Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia
Cairns R:
Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia
Lykopoulou L:
First Department of Pediatrics, University of Athens, Aghia Sofia Children's Hospital, 11527 Athens, Greece
Grinberg-Vaisman DR:
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, CIBERER, IBUB, 08028 Barcelona, Spain
Vilageliu L:
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, CIBERER, IBUB, 08028 Barcelona, Spain
Bosch M:
Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Heeren J:
Department of Biochemistry and Molecular Biology II. Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Blasi J:
Department of Pathology and Experimental Therapeutics, IDIBELL-University of Barcelona, L'Hospitalet de Llobregat, 08907 Barcelona, Spain
Timpson P:
Garvan Institute of Medical Research and Kinghorn Cancer Centre, Cancer Research Program, St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
Pol A:
Institució Catalana de Recerca i Estudis Avaçats (ICREA), 08010 Barcelona, Spain
Tebar F:
Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Murray RZ:
Tissue Repair and Regeneration Program, Institute of Health and Biomedical, Innovation, Queensland University of Technology, Brisbane, QLD 4095, Australia
Grewal T:
Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
Enrich C:
Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
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