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

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. 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. Apolipoprotein A-I (apoA-I) 5The abbreviations used are: apoA-I, apolipoprotein A-I; ABCA1, ATP-binding cassette transporter A1; MCD, methyl-β-cyclodextrin; YFP, yellow fluorescent protein; GFP, green fluorescent protein; EGF, epidermal growth factor; DiIC18, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate; BHK, baby hamster kidney; DMEM, Dulbecco's modified Eagle's medium; BSA, bovine serum albumin; PBS, phosphate-buffered saline; Tricine, N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine; wt, wild type. -mediated lipid efflux is one of the earliest events in reverse cholesterol transport, a process that generates high density lipoprotein and transports excess cholesterol from the peripheral tissues, including the arterial wall, to the liver for biliary secretion. This process is absent in Tangier disease, due to mutations in ABCA1 (1Brooks-Wilson A. Marcil M. Clee S.M. Zhang L.H. Roomp K. van Dam M. Yu L. Brewer C. Collins J.A. Molhuizen H.O. Loubser O. Ouelette B.F. Fichter K. Ashbourne-Excoffon K.J. Sensen C.W. Scherer S. Mott S. Denis M. Martindale D. Frohlich J. Morgan K. Koop B. Pimstone S. Kastelein J.J. Hayden M.R. Nat. Genet. 1999; 22: 336-345Crossref PubMed Scopus (1509) Google Scholar). Without a functional ABCA1, apoA-I is rapidly catabolized, leading to cholesterol accumulation in peripheral tissues and low plasma high density lipoprotein. ABCA1 therefore plays a key role in cholesterol efflux to lipid-poor lipoproteins, such as apoA-I. There has been considerable debate as to whether ABCA1 mediates apoA-I acquisition of phospholipids and cholesterol separately or simultaneously. In a “two-step model,” lipid-poor apoA-I firstly forms a high affinity complex with ABCA1 (2Fitzgerald M.L. Morris A.L. Rhee J.S. Andersson L.P. Mendez A.J. Freeman M.W. J. Biol. Chem. 2002; 277: 33178-33187Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar, 3Oram J.F. Lawn R.M. Garvin M.R. Wade D.P. J. Biol. Chem. 2000; 275: 34508-34511Abstract Full Text Full Text PDF PubMed Scopus (476) Google Scholar, 4Wang N. Silver D.L. Costet P. Tall A.R. J. Biol. Chem. 2000; 275: 33053-33058Abstract Full Text Full Text PDF PubMed Scopus (512) Google Scholar), which facilitates apoA-I association with phospholipid-rich domains. Second, this phospholipid-primed apoA-I acquires cholesterol from cholesterol-rich domains, a process thought to be independent of ABCA1. On the other hand, Smith et al. (5Smith J.D. Le Goff W. Settle M. Brubaker G. Waelde C. Horwitz A. Oda M.N. J. Lipid Res. 2004; 45: 635-644Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar) reported that ABCA1 mediates concurrent efflux of phospholipid and cholesterol. These contrasting models demonstrate that the mechanism by which ABCA1 mediates lipid efflux to apoA-I has yet to be clarified. Interestingly, the plasma membrane bilayer is thought to contain a mosaic of tightly packed lipid microdomains termed “lipid rafts.” Commonly defined based on their insolubility in non-ionic detergents, these microdomains contain high concentrations of cholesterol, sphingolipids, caveolin, and many proteins involved in cell signaling. In terms of apoA-I-mediated efflux, these microdomains represent a conceptually attractive “in situ” reservoir of cholesterol in the plasma membrane. Despite their enrichment in cholesterol, however, these domains do not seem to play a major role in efflux, because apoA-I was shown to preferentially acquire cholesterol from the loosely packed, “non-raft” microdomains (6Drobnik W. Borsukova H. Bottcher A. Pfeiffer A. Liebisch G. Schutz G.J. Schindler H. Schmitz G. Traffic. 2002; 3: 268-278Crossref PubMed Scopus (141) Google Scholar, 7Mendez A.J. Lin G. Wade D.P. Lawn R.M. Oram J.F. J. Biol. Chem. 2001; 276: 3158-3166Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar). ABCA1 itself also appears to be localized in Triton X-100-soluble fractions (non-rafts) (7Mendez A.J. Lin G. Wade D.P. Lawn R.M. Oram J.F. J. Biol. Chem. 2001; 276: 3158-3166Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar). It is far from clear whether non-rafts are required for ABCA1-mediated cholesterol efflux. Indeed, recent work performed by Duong and colleagues (8Duong P.T. Collins H.L. Nickel M. Lund-Katz S. Rothblat G.H. Phillips M.C. J. Lipid Res. 2006; 47: 832-843Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar) further revealed a need for a better understanding of the relative contribution of these microdomains to the ABCA1-mediated formation of nascent high density lipoprotein particles. Aside from cholesterol efflux, ABCA1 has been linked to several functions on the plasma membrane, such as phagocytosis, endocytosis, and microvesiculation (9Alder-Baerens N. Muller P. Pohl A. Korte T. Hamon Y. Chimini G. Pomorski T. Herrmann A. J. Biol. Chem. 2005; 280: 26321-26329Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 10Hamon Y. Broccardo C. Chambenoit O. Luciani M.F. Toti F. Chaslin S. Freyssinet J.M. Devaux P.F. McNeish J. Marguet D. Chimini G. Nat. Cell Biol. 2000; 2: 399-406Crossref PubMed Scopus Google Scholar, M.F. Chimini G. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 2001; 276: Full Text Full Text PDF PubMed Scopus (59) Google Scholar). These that ABCA1 significant influence on the plasma membrane. It is whether ABCA1 and, this apoA-I-mediated cholesterol efflux. attractive be that ABCA1 the raft microdomains and cholesterol thus and efflux. this we in the of ABCA1 expression on membrane observed that ABCA1 microdomains and redistributes to non-raft domains. ABCA1 also ABCA1 expression Akt a process known to be to raft L. Lin J. M.L. Freeman M.R. Res. 2002; Google Scholar). also provide evidence that this membrane reorganization is on a functional of ABCA1, of ATPase-related functions in membrane Furthermore, we observed association of apoA-I with the non-raft of the plasma membrane. Our results thus provide a mechanism by which ABCA1 facilitates apoA-I cell association and cholesterol efflux by the tightly packed lipid raft and hamster cells an or ABCA1 the of a as Oram J.F. J. Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). we further ABCA1 or cells and the that of ABCA1 cells. Cell and from and Triton from cholesterol was from ABCA1 was from from was from and was from Cell and from is a and was reported to to that transports to to A. S. M. C. C. Biol. 2005; PubMed Scopus Google Scholar). was from G. of Cell cells in serum in a cells for in with and ABCA1 expression. or cells as and cells to in and for in and was a plasma by with an fluorescent of the membrane a fluorescent with a and the of an Cholesterol by and by in of the Cholesterol with the cholesterol for and the was Triton cholesterol was as cholesterol as X-100-soluble X-100-soluble Triton Triton cells in with and on for in was with in the or Triton and further on for was and the with of was with the by of was and also from cells in of a and the was as and cholesterol, cells for with Triton by a as the cells for with and the was of to cholesterol, and sphingomyelin and in a Cholesterol cells in with for to cholesterol to to with and for cholesterol efflux, cells with apoA-I for was to cells, and for with and for Cholesterol efflux was as the of the cholesterol efflux, cells also with for by of with and with for or on for the was and for was from as was as the of the of ABCA1, and cells for in and with and with ABCA1 was by a ABCA1 by an fluorescent a fluorescent with and a from ABCA1 and cells ABCA1, and cells with in to fluorescent and ABCA1 an and the of a of cholesterol was performed as S. J. Full Text Full Text PDF PubMed Scopus Google Scholar). Triton Triton of on the plasma membrane was performed as M. S. S. A. 2001; PubMed Scopus Google Scholar). from growth to and Lipid as from S. J. Cell Biol. 1999; PubMed Scopus Google Scholar). In of the in was to In cells with for with and on with Triton for Triton membranes by a by cell the and fluorescent from cell This is the of Triton fluorescent Triton in the we several of from and of fluorescent from these of used this to fluorescent Triton from the cell or of by Triton in cell be cells and to an and of the of ABCA1, and A937V cells in and with as cell in with and for cells on and with the on the cell the cells with of in for on cells with and with for on and plasma membrane a fluorescent with a a of used was based on an by et al. C. S. A. PubMed Scopus Google Scholar). ABCA1, and A937V cells to in cell and in with and for to ABCA1 expression. of the with of Tricine, and in of A. of cells was performed by for in a in of and with of a to and for to of the in of and and as from and of and in a for a was in including the plasma membrane plasma membrane fractions to and on in for on of a plasma membrane fractions with of and of and in the of a was the plasma membrane for in a and in and was from fractions in and of and by fractions for and by ABCA1, and A937V cells to in for cell of the cholesterol was performed by with for in with and for of the with of Tricine, and in of A. of cells was performed by for in a in of and with of a to and for in a to fractions and to with A. in and the fractions on of the to for was fractions of by by for the and in by of with of and was a of Akt used was based on a by et al. L. 2002; PubMed Scopus Google Scholar). ABCA1, and A937V cells to in in with and for of effectively the cells the with cells with of of the with of Triton and in of with of cells was performed by for in a in of and with of a to and for and for of with and by and was a Akt was a Akt activation was as a of plasma apoA-I in was was with by to a of of apoA-I, and used cells with and for in was cells with PBS, on for in and Triton was with and the was by the in the and in the cells was by that ABCA1 the plasma membrane microdomains to apoA-I efflux. we used a cell with a an ABCA1 cell as Oram J.F. J. Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). These cells do not ABCA1. to to ABCA1 expression expression of ABCA1 in these cells is to that of and that in with and as by not ABCA1-expressing cells a high to efflux cholesterol to apoA-I to cells, which efflux cholesterol in Y. Smith J.D. S. A. 1999; PubMed Scopus Google Scholar) or cells cholesterol in J. J. Lipid Res. 2005; Full Text Full Text PDF PubMed Scopus Google These results that ABCA1 in cells is ABCA1 in cells by that ABCA1 was on the plasma membrane. we a and or the that the cell and a and observed that ABCA1 the plasma membrane and in with Y. Broccardo C. Chambenoit O. Luciani M.F. Toti F. Chaslin S. Freyssinet J.M. Devaux P.F. McNeish J. Marguet D. Chimini G. Nat. Cell Biol. 2000; 2: 399-406Crossref PubMed Scopus Google Scholar, N. Silver D.L. C. Tall A.R. J. Biol. Chem. 2001; 276: Full Text Full Text PDF PubMed Scopus Google Scholar). of are shown in the ABCA1 also be and These structures the of the and the whether these structures represent the that ABCA1 to the plasma membrane, we cells with a general the is ABCA1 be on the plasma membrane and also This that the likely ABCA1 that through these Furthermore, we cholesterol in these cells and that cholesterol was and ABCA1-expressing cells of of the that cholesterol be to in ABCA1 cells, which cholesterol in the plasma membrane in cholesterol, we cells with that in cell that ABCA1 expression not cholesterol content or Furthermore, we cell in these cells to the cholesterol shown in demonstrate that the plasma membrane is as by and is the cholesterol. There is major in the cell consistent with ABCA1-expressing cells, however, to cholesterol in the and or A937V cells, which cholesterol from membranes to the plasma membrane upon ABCA1 expression. these results demonstrate that of ABCA1 is localized on the plasma membrane and its expression not significant cholesterol also a cell that a of ABCA1 upon These cells a of ABCA1 and as ABCA1 Cholesterol in cells was also to that of ABCA1-expressing or cells and A937V a mutation in its ATP-binding and is not to mediate cholesterol efflux whether ABCA1 expression the of the plasma membrane, we cholesterol in terms of tightly packed membrane fractions loosely packed fractions a used the in Triton S. M. Traffic. 2004; PubMed Scopus Google Scholar), to these domains. ABCA1, and A937V cells with Triton for cholesterol in the X-100-soluble and in the cells was by In cells, of cholesterol was in Triton consistent with by that the of the plasma membrane is Triton M. S. S. A. 2001; PubMed Scopus Google Scholar, Y. M. Y. Silver D.L. C. Tall A.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Interestingly, in ABCA1 cells, we cholesterol in the Triton X-100-soluble also used to the cells and with Triton that ABCA1 cells by Triton cells ABCA1 expression not influence in Triton not This that ABCA1 cells the non-raft cholesterol change in cholesterol or as shown in and This cholesterol redistribution to Triton X-100-soluble in ABCA1-expressing cells be by of ABCA1. in the plasma membrane, of the of the we used cells Triton cholesterol in cells was to that in cells and that cholesterol redistribution from raft to non-rafts functional ABCA1 ABCA1 has been to phospholipid-rich microdomains through its This the general lipid packing of the plasma membrane. Indeed, we that Triton of major of also in with cells Interestingly, ABCA1 expression on the of a phospholipid in non-raft domains the A937V to redistribute consistent with its to redistribute cholesterol in these cells. the general of ABCA1 expression on the packing of the plasma membrane. the plasma membrane, cells with DiIC18, a fluorescent of phospholipids M. S. S. A. 2001; PubMed Scopus Google Scholar) and Triton a of the plasma membrane the of the plasma membrane. that the plasma membrane of ABCA1 cells Triton that of cells and performed on a of cells revealed that Triton as of the plasma membrane from ABCA1-expressing cells from cells to This that not also the plasma membrane as a is to Triton upon ABCA1 expression. the that ABCA1 redistributes from raft to non-raft membrane we used a used of to the of ABCA1 expression. this is not therefore to a to is a known raft/caveolae and its is to cholesterol content and the lipid of the membrane J. Cell Biol. PubMed Scopus Google Scholar, P. J. J. Cell Biol. PubMed Scopus Google Scholar). ABCA1, and A937V cells with the role of in cholesterol efflux has been the cell models to Y. A. G. D. J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar), we cholesterol efflux in cells. that significant influence on cholesterol efflux in cells This that expression itself not likely cholesterol in these cells. the in cells. we that in cells was and on the of the cells of the reported on the plasma membrane T. J. Cell 2002; PubMed Scopus Google Scholar). was to structures in these cells the B. K. K. Cell Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). In ABCA1-expressing cells, of was on the general area of the plasma membrane, caveolae-like structures and Furthermore, we the cell to their we that of ABCA1 cells a on the plasma membrane, cells of an in cells by results Moreover, in ABCA1 cells was to that of cells a by ABCA1 expression. further that redistribution from ABCA1 we cells with ABCA1. of the the cells in terms of ABCA1 expression. that the plasma membrane in cells ABCA1 and cells a and In cells and that ABCA1, was observed in and to cells Furthermore, we ABCA1 A937V, we that A937V was localized on the plasma membrane and to ABCA1 this to redistribute in A937V cells was to that in cells. This is consistent with that A937V is in rafts is known to be to cholesterol in the plasma membrane, we not in terms of cholesterol or cholesterol these cell therefore to that a in lipid packing in ABCA1 cells, such as significant of non-raft membrane from because tightly packed lipid ABCA1 likely cholesterol from therefore from to the general area of the plasma membrane H. M. J. P. Biol. PubMed Scopus Google Scholar). redistribution in ABCA1 cells, is consistent with Interestingly, we cells with apoA-I for we not on in or ABCA1 cells such as cholesterol by with MCD, a known to cholesterol and from the to the general area of the plasma membrane in cells. on in ABCA1 cells. we cholesterol these cells by a complex to rafts we in ABCA1 cells in cells not results from cells the that ABCA1 the of the plasma membrane. in ABCA1 is due to membrane lipid this also used to therefore performed a on ABCA1, and A937V cells that the of was in fractions of of was in fractions with a non-raft in and A937V cells. was in the non-raft fractions in ABCA1 cells or A937V cells There was significant and A937V cells. in is in with in cells. are thought to be in whether such from raft to non-raft in ABCA1-expressing cells cell we Akt a process known to be to L. Lin J. M.L. Freeman M.R. Res. 2002; Google Scholar). shown in a with Akt in cells as by we Akt in ABCA1 cells of A937V not Akt activation of Akt in cell of Akt Akt is shown in This a of Akt activation upon ABCA1 expression. ABCA1 therefore on Akt due to its in raft to non-raft likely of loosely packed membranes is that better to cholesterol. we performed and with cholesterol from the plasma membrane significant of S. S. P. C. S. A. 2000; PubMed Scopus Google Scholar). that was and from cells, ABCA1, and cells This that is in terms of plasma membrane cholesterol content in ABCA1 and cells. It is also consistent with that cholesterol efflux is independent of ABCA1 B. Denis M. L. Marcil M. J. J. Lipid Res. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, Rothblat G.H. G. McNeish J. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar, J.A. H. Brewer Biol. PubMed Scopus Google Scholar). these however, the high of such as therefore to a low that the of in the plasma membrane rafts from non-rafts the the by which cholesterol, thus the mechanism to we performed on we that was Interestingly, cholesterol from ABCA1 cells from cells the of results These thus the that cholesterol in the plasma membrane of ABCA1-expressing cells is to consistent with its non-raft non-raft fractions in ABCA1-expressing cells functional in terms of cholesterol efflux. has been to acquire from non-raft membrane fractions (7Mendez A.J. Lin G. Wade D.P. Lawn R.M. Oram J.F. J. Biol. Chem. 2001; 276: 3158-3166Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar), and an non-raft membrane apoA-I this we membrane domains with which apoA-I cells with for and performed Triton in ABCA1 cells that apoA-I is preferentially with non-raft membrane fractions such be observed in cells. This for a role of ABCA1 in the association of apoA-I with non-raft results that ABCA1 the functional of cholesterol, and apoA-I in loosely packed lipid microdomains of the plasma membrane. This is likely by non-raft In the we several of evidence that ABCA1 expression the general packing of the plasma membrane by loosely packed microdomains ABCA1 expression the Triton of cholesterol and Second, revealed an of the plasma membrane area by Triton in ABCA1-expressing cells. upon expression of ABCA1, was of This is also consistent with in ABCA1-expressing cells, was in non-raft fractions by cholesterol was to from ABCA1-expressing cells. Interestingly, ABCA1 expression also Akt a known we that a functional in ABCA1 is required for non-raft because the A937V to cholesterol, sphingomyelin, or A937V also to Akt These demonstrate through its ATPase-related ABCA1 the plasma membrane and generates loosely packed domains. These loosely packed domains likely apoA-I association with cells and, lipid acquisition by apoA-I to nascent high density lipoprotein particles. results on (7Mendez A.J. Lin G. Wade D.P. Lawn R.M. Oram J.F. J. Biol. Chem. 2001; 276: 3158-3166Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar, Oram J.F. J. Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). In and cells, ABCA1 expression was to cholesterol Cholesterol was to cholesterol in ABCA1-expressing cells. cells of cholesterol on membrane cholesterol is thought to on the of the and loosely packed cholesterol is likely to M. 2004; PubMed Scopus Google Scholar, Y. J. S. A. 2004; PubMed Scopus Google Scholar). Our results thus that a of cholesterol to in ABCA1-expressing cells an of cholesterol in we non-raft Interestingly, cholesterol by apoA-I in ABCA1 cells was to be from the membrane domains (7Mendez A.J. Lin G. Wade D.P. Lawn R.M. Oram J.F. J. Biol. Chem. 2001; 276: 3158-3166Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar, Oram J.F. J. Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). results therefore the that ABCA1-mediated of non-raft microdomains facilitates lipid efflux to apoA-I. It has been that the plasma membrane is a many microdomains K. 2000; PubMed Scopus Google Scholar). are to this complex the plasma membrane. been defined by Full Text PDF PubMed Scopus Google Scholar). ABCA1 appears to be localized in ABCA1 expands the non-raft fractions is not this to be independent of apoA-I, likely functions of ABCA1 on the membrane. ABCA1 influence membrane by an with domains and non-raft ABCA1 phospholipids and cholesterol from the to leading to membrane Our with the A937V seem to this of non-raft microdomains to be we show that cells a significant of the plasma membrane that was Triton apoA-I-mediated cholesterol efflux is absent in these cells. for this is that a apoA-I and ABCA1 be required for lipid acquisition from non-rafts. as a that ABCA1 non-raft domains from in cells. In cells, the packing lipid of the non-rafts in cells from in lipid efflux. we are by that further in the and of these membrane S. M. Traffic. 2004; PubMed Scopus Google Scholar). that ABCA1 on the understanding of the apoA-I-mediated lipid efflux. et al. K. H. Chimini G. 2000; PubMed Scopus Google Scholar) reported that cholesterol efflux is in cells that do not ABCA1 apoA-I was with This ABCA1 required for cholesterol efflux. that ABCA1 plays a major role in the of cholesterol to by apoA-I, therefore also to the of the efflux This also Smith et al. (5Smith J.D. Le Goff W. Settle M. Brubaker G. Waelde C. Horwitz A. Oda M.N. J. Lipid Res. 2004; 45: 635-644Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar) reported in phospholipid from cholesterol efflux. apoA-I and cholesterol in loosely packed lipid ABCA1 phospholipid and cholesterol efflux, to be separately a Our also general microdomains are thought to be significant in cells by to proteins K. D. Nat. Cell Biol. 2000; PubMed Scopus Google Scholar). Our results the that such in cell membrane are P. K. G. M. S. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar) and, far from S. M. Traffic. 2004; PubMed Scopus Google Scholar). In to which are in membranes in cells are to are from and to these lipid in the membrane are also rapidly In addition, membranes with such as the plasma membrane, to be by a of through of of the plasma membrane likely results from these It is thus not that the of membranes in cells are to from that of the Such to cells, also rafts are and as we S. M. Traffic. 2004; PubMed Scopus Google Scholar). In the for the that ABCA1 is of the microdomains on the plasma membrane, such that are non-raft microdomains upon ABCA1 expression. this reorganization on its domains. apoA-I is with non-raft membrane we that this of non-raft microdomains plays a role in apoA-I-mediated cholesterol efflux. ABCA1 likely pre-conditions cells and generates a membrane for apoA-I to acquire including cholesterol. are to the for ABCA1 to this Such to membrane microdomains represent a general mechanism for cells to functional membrane and F. Oram for the and for in Akt signaling. with

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