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

J. Biol. Chem., Vol. 281, Issue 47, 36091-36101, November 24, 2006

This Article Full Text Full Text (PDF) Supplemental Data Supplemental Data All Versions of this Article: 281/47/36091    most recent M602247200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Landry, Y. D. Articles by Zha, X. Search for Related Content PubMed PubMed Citation Articles by Landry, Y. D. Articles by Zha, X. Social Bookmarking                      What's this?

ATP-binding Cassette Transporter A1 Expression Disrupts Raft Membrane Microdomains through Its ATPase-related Functions^*

Yves D. Landry¹, Maxime Denis¹², Shilpi Nandi, Stephanie Bell³, Ashley M. Vaughan, and Xiaohui Zha⁴

From the Ottawa Health Research Institute and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1Y 4E9, Canada and the Department of Medicine, University of Washington, Seattle, Washington 98195-6426

ATP-binding cassette transporter A1 (ABCA1) is known to mediate cholesterol efflux to lipid-poor apolipoprotein A-I. In addition, ABCA1 has been shown to influence functions of the plasma membrane, such as endocytosis and phagocytosis. Here, we report that ABCA1 expression results in a significant redistribution of cholesterol and sphingomyelin from rafts to non-rafts. Caveolin, a raft/caveolae marker also redistributes from punctate caveolae-like structures to the general area of the plasma membrane upon ABCA1 expression. Furthermore, we observed significant reduction of Akt activation in ABCA1-expressing cells, consistent with raft disruption. Cholesterol content in the plasma membrane is, however, not altered. Moreover, we provide evidence that a non-functional ABCA1 with mutation in an ATP-binding domain, A937V, fails to redistribute cholesterol, sphingomyelin, or caveolin. A937V also fails to influence Akt activation. Finally, we show that apolipoprotein A-I preferentially associates with non-raft membranes in ABCA1-expressing cells. Our results thus demonstrate that ABCA1 causes a change in overall lipid packing of the plasma membrane, likely through its ATPase-related functions. Such reorganization by ABCA1 effectively expands the non-raft membrane fractions and, consequentially, pre-conditions cells for cholesterol efflux.

Received for publication, March 9, 2006 , and in revised form, September 18, 2006.

^* This work is supported in part by grants from the Heart and Stroke Foundation of Canada (New Investigator Award), the Heart and Stroke Foundation of Ontario (Grant NA5246), and the Canada Innovation Foundation/Ontario Innovation Trust and by a start-up fund from the Ottawa Health Research Institute. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Movies S1-S4.

¹ Both authors contributed equally to this work.

² Supported by a postdoctoral fellowship from Canadian Institutes of Health Research.

³ Supported by a John D. Schultz Science Student Scholarship from Heart and Stroke Foundation of Ontario.

⁴ To whom correspondence should be addressed: Ottawa Health Research Institute and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 725 Parkdale Avenue, Ottawa, Ontario K1Y 4E9, Canada. Tel.: 613-798-5555 (ext. 19828); Fax: 613-761-5036; E-mail: xzha{at}ohri.ca.

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

This article has been cited by other articles:

				K. Nagao, Y. Zhao, K. Takahashi, Y. Kimura, and K. Ueda Sodium taurocholate-dependent lipid efflux by ABCA1: effects of W590S mutation on lipid translocation and apolipoprotein A-I dissociation J. Lipid Res., June 1, 2009; 50(6): 1165 - 1172. [Abstract] [Full Text] [PDF]

				A. Zarubica, A. P. Plazzo, M. Stockl, T. Trombik, Y. Hamon, P. Muller, T. Pomorski, A. Herrmann, and G. Chimini Functional implications of the influence of ABCA1 on lipid microenvironment at the plasma membrane: a biophysical study FASEB J, June 1, 2009; 23(6): 1775 - 1785. [Abstract] [Full Text] [PDF]

				S. Nandi, L. Ma, M. Denis, J. Karwatsky, Z. Li, X.-C. Jiang, and X. Zha ABCA1-mediated cholesterol efflux generates microparticles in addition to HDL through processes governed by membrane rigidity J. Lipid Res., March 1, 2009; 50(3): 456 - 466. [Abstract] [Full Text] [PDF]

				A. M. Vaughan, C. Tang, and J. F. Oram ABCA1 mutants reveal an interdependency between lipid export function, apoA-I binding activity, and Janus kinase 2 activation J. Lipid Res., February 1, 2009; 50(2): 285 - 292. [Abstract] [Full Text] [PDF]

				M. Stockl, A. P. Plazzo, T. Korte, and A. Herrmann Detection of Lipid Domains in Model and Cell Membranes by Fluorescence Lifetime Imaging Microscopy of Fluorescent Lipid Analogues J. Biol. Chem., November 7, 2008; 283(45): 30828 - 30837. [Abstract] [Full Text] [PDF]

				X. Zhu, J.-Y. Lee, J. M. Timmins, J. M. Brown, E. Boudyguina, A. Mulya, A. K. Gebre, M. C. Willingham, E. M. Hiltbold, N. Mishra, et al. Increased Cellular Free Cholesterol in Macrophage-specific Abca1 Knock-out Mice Enhances Pro-inflammatory Response of Macrophages J. Biol. Chem., August 22, 2008; 283(34): 22930 - 22941. [Abstract] [Full Text] [PDF]

				K. Bowden and N. D. Ridgway OSBP Negatively Regulates ABCA1 Protein Stability J. Biol. Chem., June 27, 2008; 283(26): 18210 - 18217. [Abstract] [Full Text] [PDF]

				M. Denis, Y. D. Landry, and X. Zha ATP-binding Cassette A1-mediated Lipidation of Apolipoprotein A-I Occurs at the Plasma Membrane and Not in the Endocytic Compartments J. Biol. Chem., June 6, 2008; 283(23): 16178 - 16186. [Abstract] [Full Text] [PDF]

				L. E. Faulkner, S. E. Panagotopulos, J. D. Johnson, L. A. Woollett, D. Y. Hui, S. R. Witting, J. N. Maiorano, and W. S. Davidson An analysis of the role of a retroendocytosis pathway in ABCA1-mediated cholesterol efflux from macrophages J. Lipid Res., June 1, 2008; 49(6): 1322 - 1332. [Abstract] [Full Text] [PDF]

				S. R. Bates, J.-Q. Tao, K. J. Yu, Z. Borok, E. D. Crandall, H. L. Collins, and G. H. Rothblat Expression and Biological Activity of ABCA1 in Alveolar Epithelial Cells Am. J. Respir. Cell Mol. Biol., March 1, 2008; 38(3): 283 - 292. [Abstract] [Full Text] [PDF]

				H. H. Hassan, M. Denis, D.-Y. D. Lee, I. Iatan, D. Nyholt, I. Ruel, L. Krimbou, and J. Genest Identification of an ABCA1-dependent phospholipid-rich plasma membrane apolipoprotein A-I binding site for nascent HDL formation: implications for current models of HDL biogenesis J. Lipid Res., November 1, 2007; 48(11): 2428 - 2442. [Abstract] [Full Text] [PDF]

				C. Vedhachalam, P. T. Duong, M. Nickel, D. Nguyen, P. Dhanasekaran, H. Saito, G. H. Rothblat, S. Lund-Katz, and M. C. Phillips Mechanism of ATP-binding Cassette Transporter A1-mediated Cellular Lipid Efflux to Apolipoprotein A-I and Formation of High Density Lipoprotein Particles J. Biol. Chem., August 24, 2007; 282(34): 25123 - 25130. [Abstract] [Full Text] [PDF]

				J. M. Kinchen and K. S. Ravichandran Journey to the grave: signaling events regulating removal of apoptotic cells J. Cell Sci., July 1, 2007; 120(13): 2143 - 2149. [Abstract] [Full Text] [PDF]

				C. Vedhachalam, A. B. Ghering, W. S. Davidson, S. Lund-Katz, G. H. Rothblat, and M. C. Phillips ABCA1-Induced Cell Surface Binding Sites for ApoA-I Arterioscler. Thromb. Vasc. Biol., July 1, 2007; 27(7): 1603 - 1609. [Abstract] [Full Text] [PDF]

				K. Nagao, K. Takahashi, K. Hanada, N. Kioka, M. Matsuo, and K. Ueda Enhanced ApoA-I-dependent Cholesterol Efflux by ABCA1 from Sphingomyelin-deficient Chinese Hamster Ovary Cells J. Biol. Chem., May 18, 2007; 282(20): 14868 - 14874. [Abstract] [Full Text] [PDF]

				Y. Wang and J. F. Oram Unsaturated fatty acids phosphorylate and destabilize ABCA1 through a protein kinase C {delta} pathway J. Lipid Res., May 1, 2007; 48(5): 1062 - 1068. [Abstract] [Full Text] [PDF]

				M. Fukuda, M. Nakano, S. Sriwongsitanont, M. Ueno, Y. Kuroda, and T. Handa Spontaneous reconstitution of discoidal HDL from sphingomyelin-containing model membranes by apolipoprotein A-I J. Lipid Res., April 1, 2007; 48(4): 882 - 889. [Abstract] [Full Text] [PDF]