HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Papers In Press, published online ahead of print June 1, 2009
J. Lipid Res., doi:10.1194/jlr.M800597-JLR200

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: M800597-JLR200v1 50/6/1165    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nagao, K. Articles by Ueda, K. Search for Related Content PubMed PubMed Citation Articles by Nagao, K. Articles by Ueda, K. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 50, 1165-1172, June 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Sodium taurocholate-dependent lipid efflux by ABCA1: effects of W590S mutation on lipid translocation and apolipoprotein A-I dissociation

Kohjiro Nagao^*, Yu Zhao^*, Kei Takahashi^*, Yasuhisa Kimura^* and Kazumitsu Ueda^1,*,

^* Laboratory of Cellular Biochemistry, Division of Applied Life Sciences, Kyoto University Graduate School of Agriculture, Kyoto 606-8502, Japan
Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8502, Japan

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of eight figures.

This work was supported by a Grant-in-aid for Scientific research (S) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation. This work was supported by the World Premier International Research Center Initiative, MEXT, Japan.

Published, JLR Papers in Press, February 8, 2009.

¹ To whom correspondence should be addressed. e-mail: uedak{at}kais.kyoto-u.ac.jp

ABCA1 plays a major role in HDL metabolism. Cholesterol secretion by ABCA1 is dependent on the presence of extracellular acceptors, such as lipid-free apolipoprotein A-I (apoA-I). However, the importance of the direct interaction between apoA-I and ABCA1 in HDL formation remains unclear. In contrast, ABCB4 mediates the secretion of phospholipids and cholesterol in the presence of sodium taurocholate (NaTC) but not in the presence of apoA-I. In this study, we analyzed apoA-I binding and NaTC-dependent lipid efflux by ABCA1. ABCA1 mediated the efflux of cholesterol and phospholipids in the presence of NaTC as well as in the presence of apoA-I in an ATP-dependent manner. The Tangier disease mutation W590S, which resides in the extracellular domain and impairs apoA-I-dependent lipid efflux, greatly decreased NaTC-dependent cholesterol and phospholipid efflux. However, the W590S mutation did not impair apoA-I binding and, conversely, retarded the dissociation of apoA-I from ABCA1. These results suggest that the W590S mutation impairs ATP-dependent lipid translocation and that lipid translocation or possibly lipid loading, facilitates apoA-I dissociation from ABCA1. NaTC is a good tool for analyzing ABCA1-mediated lipid efflux and allows dissection of the steps of HDL formation by ABCA1.

Supplementary key words cholesterol • HDL • Tangier disease

Abbreviations: ABC, ATP binding cassette; apoA-I, apolipoprotein A-I; GFP, green fluorescent protein; HEK, human embryonic kidney; MβCD, methyl-β-cyclodexitrin; NaTC, sodium taurocholate; PC, phosphatidylcholine; RA, 9 cis-retinoic acid; sulfo-NHS-biotin, sulfo-N-hydroxysuccinimidobiotin

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?