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 March 1, 2009
J. Lipid Res., doi:10.1194/jlr.M800345-JLR200

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: M800345-JLR200v1 50/3/456    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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Nandi, S. Articles by Zha, X. Search for Related Content PubMed PubMed Citation Articles by Nandi, S. Articles by Zha, X. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 50, 456-466, March 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

ABCA1-mediated cholesterol efflux generates microparticles in addition to HDL through processes governed by membrane rigidity

Shilpi Nandi^*, Loretta Ma^*, Maxime Denis^*, Joel Karwatsky^*, Zhiqiang Li, Xian-Cheng Jiang and Xiaohui Zha^1,*

^* Ottawa Health Research Institute and Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario K1Y 4E9, Canada
SUNY Downstate Medical Center, Brooklyn, NY 11203

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

This work is supported by grants from Heart and Stroke Foundation of Canada (New Investigator Award), Canadian Institutes of Health Research and Canada Innovation Foundation/Ontario Innovation Trust. L.M. acknowledges an Ontario Scholarship in Science and Technology. M. D. and J. K. are supported by a Canadian Institutes of Health Research postdoctoral fellowship and by a Heart and Stroke Foundation of Canada/AstraZeneca postdoctoral fellowship, respectively.

Published, JLR Papers in Press, October 21, 2008.

¹ To whom correspondence should be addressed. e-mail: xzha{at}ohri.ca

ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-poor apolipoprotein A-I (apoA-I) and generates HDL. Here, we demonstrate that ABCA1 also directly mediates the production of apoA-I free microparticles. In baby hamster kidney (BHK) cells and RAW macrophages, ABCA1 expression led to lipid efflux in the absence of apoA-I and released large microparticles devoid of apoB and apoE. We provide evidence that these microparticles are an integral component of the classical cholesterol efflux pathway when apoA-I is present and accounted for approximately 30% of the total cholesterol released to the medium. Furthermore, microparticle release required similar ABCA1 activities as was required for HDL production. For instance, a nucleotide binding domain mutation in ABCA1 (A937V) that impaired HDL generation also abolished microparticle release. Similarly, inhibition of protein kinase A (PKA) prevented the release of both types of particles. Interestingly, physical modulation of membrane dynamics affected HDL and microparticle production, rigidifying the plasma membrane with wheat germ agglutinin inhibited HDL and microparticle release, whereas increasing the fluidity promoted the production of these particles. Given the established role of ABCA1 in expending nonraft or more fluid-like membrane domains, our results suggest that both HDL and microparticle release is favored by a more fluid plasma membrane. We speculate that ABCA1 enhances the dynamic movement of the plasma membrane, which is required for apoA-I lipidation and microparticle formation.

Supplementary key words apoA-I • macrophages • wheat germ agglutinin • plasma membrane

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

This article has been cited by other articles:

				L. Yvan-Charvet, N. Wang, and A. R. Tall Role of HDL, ABCA1, and ABCG1 Transporters in Cholesterol Efflux and Immune Responses Arterioscler Thromb Vasc Biol, February 1, 2010; 30(2): 139 - 143. [Abstract] [Full Text] [PDF]