| Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function. | |
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MedLine Citation:
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PMID: 22039070 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Cholesterol regulates plasma membrane (PM) association and functioning of syntaxin-4 and soluble N-ethylmaleimide-sensitive fusion protein 23 (SNAP23) in the secretory pathway. However, the molecular mechanism and cellular cholesterol pools that determine the localization and assembly of these target membrane SNAP receptors (t-SNAREs) are largely unknown. We recently demonstrated that high levels of annexin A6 (AnxA6) induce accumulation of cholesterol in late endosomes, thereby reducing cholesterol in the Golgi and PM. This leads to an impaired supply of cholesterol needed for cytosolic phospholipase A(2) (cPLA(2)) to drive Golgi vesiculation and caveolin transport to the cell surface. Using AnxA6-overexpressing cells as a model for cellular cholesterol imbalance, we identify impaired cholesterol egress from late endosomes and diminution of Golgi cholesterol as correlating with the sequestration of SNAP23/syntaxin-4 in Golgi membranes. Pharmacological accumulation of late endosomal cholesterol and cPLA(2) inhibition induces a similar phenotype in control cells with low AnxA6 levels. Ectopic expression of Niemann-Pick C1 (NPC1) or exogenous cholesterol restores the location of SNAP23 and syntaxin-4 within the PM. Importantly, AnxA6-mediated mislocalization of these t-SNAREs correlates with reduced secretion of cargo via the SNAP23/syntaxin-4-dependent constitutive exocytic pathway. We thus conclude that inhibition of late endosomal export and Golgi cholesterol depletion modulate t-SNARE localization and functioning along the exocytic pathway. |
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Authors:
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Meritxell Reverter; Carles Rentero; Sandra Vilà de Muga; Anna Alvarez-Guaita; Vishwaroop Mulay; Rose Cairns; Peta Wood; Katia Monastyrskaya; Albert Pol; Francesc Tebar; Joan Blasi; Thomas Grewal; Carlos Enrich |
Publication Detail:
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Type: JOURNAL ARTICLE |
Journal Detail:
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Title: Molecular biology of the cell Volume: 22 ISSN: 1939-4586 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-10-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: - |
Other Details:
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Languages: ENG Pagination: 4108-4123 Citation Subset: - |
Affiliation:
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Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia Urology Research Laboratory, Department of Clinical Research, University of Bern, 3000 Bern 9, Switzerland Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain Department of Pathology and Experimental Therapeutics, IDIBELL-University of Barcelona, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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