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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wang, Li-juan Ge, Liang Li, Bo-liang Miao, Hong-hua Qi, Wei Qu, Yu-xiu Song, Bao-liang |
| Description | Author Affiliation: Ge L ( State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.); |
| Abstract | Dietary absorption is a major way for mammals to obtain cholesterol, which is mediated by Niemann-Pick C1-like 1 (NPC1L1) via vesicular endocytosis. One fundamental question in this process is how free cholesterol is efficiently taken up through the internalization of NPC1L1. Using exogenously expressed NPC1L1-EGFP, we show that the lipid raft proteins flotillins associate with NPC1L1 and their localization is regulated by NPC1L1 during intracellular trafficking. Furthermore, flotillins are essential for NPC1L1-mediated cellular cholesterol uptake, biliary cholesterol reabsorption, and the regulation of lipid levels in mice. Together with NPC1L1, they form cholesterol-enriched membrane microdomains, which function as carriers for bulk of cholesterol. The hypocholesterolemic drug ezetimibe disrupts the association between NPC1L1 and flotillins, which blocks the formation of the cholesterol-enriched microdomains. Our findings reveal a functional role of flotillins in NPC1L1-mediated cholesterol uptake and elucidate the formation of NPC1L1-flotillins-postive cholesterol-enriched membrane microdomains as a mechanism for efficient cholesterol absorption. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cholesterol Metabolism Membrane Proteins Niemann-Pick Diseases Animals Anticholesteremic Agents Pharmacology Azetidines Chemistry Ezetimibe Green Fluorescent Proteins Homeostasis Membrane Transport Proteins Mice Microscopy, Confocal Microscopy, Fluorescence Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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