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

A team of researchers, led by Prof. SONG Baoliang, from Shanghai Institute of Biochemistry and Cell Biology (SIBCB), discovered that Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol uptake.

 

Excessive cholesterol intake is one of the major risk factors leading to hypercholesterolemia and cardiovascular diseases, especially atherosclerosis. Dietary absorption is a major way for mammals to obtain cholesterol, which is essentially 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, Prof. Song’s group found that the lipid raft proteins flotillins associate with NPC1L1 and their localization is regulated by NPC1L1 during intracellular trafficking. Furthermore, the researchers demonstrated that flotillins are essential for NPC1L1-mediated cellular cholesterol uptake, biliary cholesterol reabsorption, and the regulation of lipid levels in mice. Flotillins and NPC1L1 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. Their 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.

 

The research was published online in Proceedings of the National Academy of Sciences on December 28th, 2010.

 

This work was supported by grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China, the Chinese Academy of Sciences, and the Science and Technology Commission of Shanghai Municipality. (SIBCB)

 

AUTHOR CONTACT:

SONG Baoliang, Ph.D.

Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Telephone: +86- 21-54921649 ; E-mail: blsong@sibs.ac.cn