Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol uptake

	Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol uptake
	Ge, LA; Qi, W; Wang, LJ; Miao, HH; Qu, YX; Li, BL; Song, BL
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2011
卷号	108 期号:2 页码:551-556
通讯作者	Song, BL (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,blsong@sibs.ac.cn
英文摘要	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.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	REGGIE/FLOTILLIN PROTEINS ; REGULATED TRANSLOCATION ; CELL-SURFACE ; NPC1L1 ; MEMBRANE ; MICRODOMAINS ; ABSORPTION ; EZETIMIBE ; CAVEOLAE ; RAFTS
收录类别	SCI
语种	英语
WOS记录号	WOS:000286097700026
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/758]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Ge, LA,Qi, W,Wang, LJ,et al. Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol uptake[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2011,108(2):551-556.
APA	Ge, LA.,Qi, W.,Wang, LJ.,Miao, HH.,Qu, YX.,...&Song, BL.(2011).Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol uptake.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,108(2),551-556.
MLA	Ge, LA,et al."Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol uptake".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108.2(2011):551-556.