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

• DOI: 10.1073/pnas.1014434108
• Publication Date: 2010-12-28T01:45:14Z
• Authors: Liang Ge; Wei Qi; Li-Juan Wang; Hong-Hua Miao; Yu-Xiu Qu; Bo-Liang Li; Bao-Liang Song
• Keywords: Ezetimibe; Internalization; Lipid raft

Dietary absorption is a major way for mammals to obtain cholesterol, which mediated by Niemann-Pick C1-like 1 (NPC1L1) via vesicular endocytosis. One fundamental question in this process how free cholesterol efficiently taken up through the internalization of NPC1L1. Using exogenously expressed NPC1L1-EGFP, we show that lipid raft proteins flotillins associate with NPC1L1 and their localization regulated during intracellular trafficking. Furthermore, are essential NPC1L1-mediated cellular uptake, biliary reabsorption, regulation levels mice. Together NPC1L1, they form cholesterol-enriched membrane microdomains, function as carriers bulk cholesterol. The hypocholesterolemic drug ezetimibe disrupts association between flotillins, blocks formation microdomains. Our findings reveal functional role uptake elucidate NPC1L1–flotillins-postive microdomains mechanism efficient absorption.