| STARD4 abundance regulates sterol transport and sensing. | |
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MedLine Citation:
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PMID: 21900492 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Non-vesicular transport of cholesterol plays an essential role in the distribution and regulation of cholesterol within cells, but it has been difficult to identify the key intracellular cholesterol transporters. The StAR-related lipid transfer (START) family of proteins is involved in several pathways of non-vesicular trafficking of sterols. Among them, STARD4 has been shown to increase intracellular cholesteryl ester formation and is controlled at the transcriptional level by sterol levels in cells. We found that STARD4 is very efficient in transporting sterol between membranes in vitro. Cholesterol levels are increased in STARD4-silenced cells, while sterol transport to the endocytic recycling compartment and to the endoplasmic reticulum are enhanced upon STARD4 overexpression. STARD4 silencing attenuates cholesterol-mediated regulation of SREBP-2 activation, while its overexpression amplifies sterol sensing by SCAP/SREBP-2. To analyze STARD4's mode of action, we compared sterol transport mediated by STARD4 with a simple sterol carrier, methyl-β-cyclodextrin, when they were overexpressed or injected in cells. Interestingly, STARD4 and cytosolic methyl-β-cyclodextrin act similarly by increasing the rate of transfer of sterol to the endocytic recycling compartment and to the endoplasmic reticulum. Our results suggest that cholesterol transport mediated by STARD4 is an important component of the cholesterol homeostasis regulatory machinery. |
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Authors:
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Bruno Mesmin; Nina H Pipalia; Frederik W Lund; Trudy F Ramlall; Anna Sokolov; David Eliezer; Frederick R Maxfield |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-7 |
Journal Detail:
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Title: Molecular biology of the cell Volume: - ISSN: 1939-4586 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-8 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: - Citation Subset: - |
Affiliation:
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Department of Biochemistry, Weill Cornell Medical College, New York, NY, USA Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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