Differential Impact of Caveolae and Caveolin-1 Scaffolds on The Membrane Raft Proteome

Caveolae, a class of cholesterol-rich lipid rafts, are smooth invaginations of the plasma membrane whose formation in nonmuscle cells requires caveolin-1 (Cav1). The recent demonstration that Cav1-associated cavin proteins, in particular PTRF/cavin-1, are also required for caveolae formation supports a functional role for Cav1 independently of caveolae. In tumor cells deficient for Golgi β-1,6N-acetylglucosaminyltransferase V (Mgat5), reduced Cav1 expression is associated not with caveolae but with oligomerized Cav1 domains, or scaffolds, that functionally regulate receptor signaling and raft-dependent endocytosis. Using subdiffraction-limit microscopy, we show that Cav1 scaffolds are homogenous subdiffraction-limit sized structures whose size distribution differs from that of Cav1 in caveolae expressing cells. These cell lines displaying differing Cav1/caveolae phenotypes are effective tools for probing the structure and composition of caveolae. Using stable isotope labeling by amino acids in cell culture, we are able to quantitatively distinguish the composition of caveolae from the background of detergent-resistant membrane proteins and show that the presence of caveolae enriches the protein composition of detergent-resistant membrane, including the recruitment of multiple heterotrimeric G-protein subunits. These data were further supported by analysis of immuno-isolated Cav1 domains and of methyl-β-cyclodextrin-disrupted detergent-resistant membrane. Our data show that loss of caveolae results in a dramatic change to the membrane raft proteome and that this change is independent of Cav1 expression. The proteomics data, in combination with subdiffraction-limit microscopy, indicates that noncaveolar Cav1 domains, or scaffolds are structurally and functionally distinct from caveolae and differentially impact on the molecular composition of lipid rafts. Caveolae, a class of cholesterol-rich lipid rafts, are smooth invaginations of the plasma membrane whose formation in nonmuscle cells requires caveolin-1 (Cav1). The recent demonstration that Cav1-associated cavin proteins, in particular PTRF/cavin-1, are also required for caveolae formation supports a functional role for Cav1 independently of caveolae. In tumor cells deficient for Golgi β-1,6N-acetylglucosaminyltransferase V (Mgat5), reduced Cav1 expression is associated not with caveolae but with oligomerized Cav1 domains, or scaffolds, that functionally regulate receptor signaling and raft-dependent endocytosis. Using subdiffraction-limit microscopy, we show that Cav1 scaffolds are homogenous subdiffraction-limit sized structures whose size distribution differs from that of Cav1 in caveolae expressing cells. These cell lines displaying differing Cav1/caveolae phenotypes are effective tools for probing the structure and composition of caveolae. Using stable isotope labeling by amino acids in cell culture, we are able to quantitatively distinguish the composition of caveolae from the background of detergent-resistant membrane proteins and show that the presence of caveolae enriches the protein composition of detergent-resistant membrane, including the recruitment of multiple heterotrimeric G-protein subunits. These data were further supported by analysis of immuno-isolated Cav1 domains and of methyl-β-cyclodextrin-disrupted detergent-resistant membrane. Our data show that loss of caveolae results in a dramatic change to the membrane raft proteome and that this change is independent of Cav1 expression. The proteomics data, in combination with subdiffraction-limit microscopy, indicates that noncaveolar Cav1 domains, or scaffolds are structurally and functionally distinct from caveolae and differentially impact on the molecular composition of lipid rafts. Plasmalemmal proteins and lipids can segregate into different subdomains, forming tightly packed, lipid-ordered phases enriched in specific subsets of proteins. Collectively known as lipid rafts, these structures can be biochemically enriched in a low-density detergent-resistant membrane (DRM) 1The abbreviations used are:Cav1Caveolin-1PTRFPolymerase I and transcript release factorMgat5Golgi β-1,6N-acetylglucosaminyltransferase VSTEDStimulated Emission Depletion microscopySILACStable Isotope Labeling by Amino acids in Cell cultureDRMsDetergent-resistant membranesEGFREpidermal Growth Factor ReceptorCT-bCholera toxin b-subunitMEFsMouse embryonic fibroblastsSDCSodium deoxycholateTx-100Triton X-100MβCDMethyl-β-cyclodextrinLC-MS/MSLiquid chromatography-tandem mass spectrometrySDPRSerum deprivation protein responseIPAIngenuity Pathways Analysis. fraction (1Zheng Y.Z. Foster L.J. Biochemical and proteomic approaches for the study of membrane microdomains.J. Proteomics. 2009; 72: 12-22Crossref PubMed Scopus (38) Google Scholar). This compartmentalization helps to coordinate various activities of raft-associated proteins (2Simons K. Ikonen E. Functional rafts in cell membranes.Nature. 1997; 387: 569-572Crossref PubMed Scopus (7948) Google Scholar, 3Brown D.A. Rose J.K. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface.Cell. 1992; 68: 533-544Abstract Full Text PDF PubMed Scopus (2588) Google Scholar), making the domains a subject of great interest for cell biologists (4Lajoie P. Nabi I.R. Lipid rafts, caveolae, and their endocytosis.Int. Rev. Cell Mol. Biol. 2010; 282: 135-163Crossref PubMed Scopus (262) Google Scholar) and proteomics scientists alike (5Foster L. Mass spectrometry outgrows simple biochemistry: new approaches to organelle proteomics.Biophys. Rev. Lett. 2006; 1: 163-175Crossref Google Scholar). Formation of caveolae, a subtype of rafts characterized by morphologically distinctive invaginations of the plasma membrane depends on the presence of the protein caveolin-1 (Cav1) (6Parton R.G. Simons K. The multiple faces of caveolae.Nat. Rev. Mol. Cell Biol. 2007; 8: 185-194Crossref PubMed Scopus (1128) Google Scholar). Recent comparative proteomic analyses of DRMs from wild-type and Cav1−/− fibroblasts identified PTRF (Polymerase I and transcript release factor) or cavin-1 as a crucial regulator of caveolae formation (7Hill M.M. Bastiani M. Luetterforst R. Kirkham M. Kirkham A. Nixon S.J. Walser P. Abankwa D. Oorschot V.M. Martin S. Hancock J.F. Parton R.G. PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function.Cell. 2008; 132: 113-124Abstract Full Text Full Text PDF PubMed Scopus (514) Google Scholar). Other cavin family proteins were subsequently identified with varying roles regulating caveolae formation, dynamics and size (8McMahon K.A. Zajicek H. Li W.P. Peyton M.J. Minna J.D. Hernandez V.J. Luby-Phelps K. Anderson R.G. SRBC/cavin-3 is a caveolin adapter protein that regulates caveolae function.EMBO J. 2009; 28: 1001-1015Crossref PubMed Scopus (158) Google Scholar, 9Bastiani M. Liu L. Hill M.M. Jedrychowski M.P. Nixon S.J. Lo H.P. Abankwa D. Luetterforst R. Fernandez-Rojo M. Breen M.R. Gygi S.P. Vinten J. Walser P.J. North K.N. Hancock J.F. Pilch P.F. Parton R.G. MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes.J. Cell Biol. 2009; 185: 1259-1273Crossref PubMed Scopus (204) Google Scholar, 10Allen J.A. Yu J.Z. Donati R.J. Rasenick M.M. Beta-adrenergic receptor stimulation promotes G alpha s internalization.Mol. Pharmacol. 2005; 67: 1493-1504Crossref PubMed Scopus (87) Google Scholar, 11Hansen C.G. Bright N.A. Howard G. Nichols B.J. SDPR induces membrane curvature and functions in the formation of caveolae.Nat. Cell Biol. 2009; 11: 807-814Crossref PubMed Scopus (194) Google Scholar). The requirement for proteins other than Cav1 in caveolae formation argues that Cav1 functions outside of caveolae (6Parton R.G. Simons K. The multiple faces of caveolae.Nat. Rev. Mol. Cell Biol. 2007; 8: 185-194Crossref PubMed Scopus (1128) Google Scholar, 14Zheng Y.Z. Berg K.B. Foster L.J. Mitochondria do not contain lipid rafts, and lipid rafts do not contain mitochondrial proteins.J. Lipid Res. 2009; 50: 988-998Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 15Head B.P. Insel P.A. Do caveolins regulate cells by actions outside of caveolae?.Trends Cell Biol. 2007; 17: 51-57Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar). Caveolin-1 Polymerase I and transcript release factor Golgi β-1,6N-acetylglucosaminyltransferase V Stimulated Emission Depletion microscopy Stable Isotope Labeling by Amino acids in Cell culture Detergent-resistant membranes Epidermal Growth Factor Receptor Cholera toxin b-subunit Mouse embryonic fibroblasts Sodium deoxycholate Triton chromatography-tandem mass spectrometry deprivation protein Pathways Analysis. these to study the composition of caveolae of a of effective contain not caveolae but other of raft domains and other from I.R. regulating caveolae.Nat. Cell Biol. 2009; 11: PubMed Scopus Google Scholar, L.J. M. proteomics of lipid rafts for signaling PubMed Scopus Google Scholar). of caveolae are as with (1Zheng Y.Z. Foster L.J. Biochemical and proteomic approaches for the study of membrane microdomains.J. Proteomics. 2009; 72: 12-22Crossref PubMed Scopus (38) Google Scholar). with of proteins can be effective to the composition of these The Golgi V for that to the of membrane the P. Nabi I.R. rafts, and of receptor signaling the plasma Cell Biol. 2009; 185: PubMed Scopus Google Scholar). tumor and formation but Cav1 expression to tumor size in that Cav1 expression on tumor in the of and the M. Nabi I.R. the cell by 2009; PubMed Scopus Google Scholar, M. J. J. R. of tumor and in PubMed Scopus Google Scholar). These to the and of cell cells from wild-type that Cav1 and cells from that Cav1 but cells from that Cav1 protein and that the by the of M. J. J. R. of tumor and in PubMed Scopus Google Scholar). that noncaveolar Cav1 in cells form molecular and Epidermal Growth Factor Receptor signaling and as as dynamics of the raft toxin b-subunit M. J. J. R. of tumor and in PubMed Scopus Google Scholar, P. G. J. A. Nabi I.R. membrane regulates signaling in tumor Cell Biol. 2007; PubMed Scopus Google Scholar). Cav1 is not associated with caveolae in the of P. S. Li L. Nabi I.R. Caveolin-1 of of independently of Mol. 2009; PubMed Scopus Google Scholar), that Cav1 scaffolds a Cav1 P. G. J. A. Nabi I.R. membrane regulates signaling in tumor Cell Biol. 2007; PubMed Scopus Google Scholar). these a caveolae, Cav1 scaffolds, and raft domains functionally distinct of lipid rafts whose expression of the of Cav1 of from a proteins, Cav1 and the protein composition of caveolae and Cav1 scaffolds we microscopy to show that Cav1 scaffolds domains whose size and distribution from that of caveolae. also the proteome of cells Cav1/caveolae Cav1 scaffolds or Cav1 or caveolae and the data with that of DRMs from wild-type and Cav1−/− embryonic Our results show that expression of Cav1 scaffolds but not caveolae proteins, including signaling G proteins, from the raft proteome that caveolae and Cav1 expression differentially on the protein composition and signaling of lipid raft The were from the and and cell culture and and and North Triton deoxycholate and and Isotope with Mouse protein Foster used and their were as The cell lines were as M. J. J. R. of tumor and in PubMed Scopus Google Scholar). and stable Isotope Labeling by Amino acids in Cell culture labeling as L.J. M. proteomics of lipid rafts for signaling PubMed Scopus Google Scholar). cells were in with and and to with and cell were in the labeling to we to the different as for the and for and and for and of cells were used for detergent-resistant membrane and the and cells were for to and cells were with for with and Cav1−/− were in as (7Hill M.M. Bastiani M. Luetterforst R. Kirkham M. Kirkham A. Nixon S.J. Walser P. Abankwa D. Oorschot V.M. Martin S. Hancock J.F. Parton R.G. PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function.Cell. 2008; 132: 113-124Abstract Full Text Full Text PDF PubMed Scopus (514) Google Scholar). of cells were used cell for detergent-resistant membrane in DRMs were from or cells as I.R. regulating caveolae.Nat. Cell Biol. 2009; 11: PubMed Scopus Google Scholar, L.J. M. proteomics of lipid rafts for signaling PubMed Scopus Google Scholar). cells were in Triton protein of cell were and of protein from were this are into and to by of of or This is in the of by of and These were for and the and is a to the of the and a to the This is with and membranes are by for to of were were from and of cells. In the and cells were in for or of Caveolin-1 or protein were to and the were for the were for with the were in in for with the protein of the were by and a protein In the cells were in and with and by a of the cells were by and cell were for and to the to DRMs and to for The of the the as the of Caveolin-1 and were of cell from and were with by to membrane and with were used as in for for and for used and with and cells were and with J.A. Yu J.Z. Donati R.J. Rasenick M.M. Beta-adrenergic receptor stimulation promotes G alpha s internalization.Mol. Pharmacol. 2005; 67: 1493-1504Crossref PubMed Scopus (87) Google Scholar) cells were with or for and with the with cells were with or as the cells were with and with for The cells were for with and with In were with and with and the were with the and were in for analysis and were from cells and the microscopy microscopy, cells were in with Triton and with with were with and in for were a of for and V for and V for and a of and of a to of structures with and the of cells to the of cells from independent analysis on to were different analyses in in with protein or protein in the in and to were reduced and as Foster L.J. The proteome and the of the 2007; PubMed Scopus Google Scholar). by of were by chromatography-tandem mass spectrometry on a The to a into on a from of and of and were from to to in the for and to for to the The to a from to in the and to the in in the In were also further by into and of or and of as Foster L.J. The proteome and the of the 2007; PubMed Scopus Google Scholar) and as on and were and to the Mouse and and were with the with to and for and as a protein or and as a mass of the mass is used to to other and the isotope and that do not the are not used in the for The in the various are the with the of the the were a of proteins identified were of data in the of is on and in these by independent of Mass and on In this of DRMs from and Cav1−/− were by with from to on a and with V and the used to the molecular and by and analysis of the molecular Mass to with in or Cav1−/− The were used in the of or mass of that in of in of that in of the cell were of to The were into and the or Cav1−/− were to in the the a specific for This on we the of of and protein are with the of proteins and identified in Mass and were Mouse used as a Other to for and for and required a protein with and P. G. J. A. Nabi I.R. membrane regulates signaling in tumor Cell Biol. 2007; PubMed Scopus Google Scholar, P. S. Li L. Nabi I.R. Caveolin-1 of of independently of Mol. 2009; PubMed Scopus Google Scholar), Cav1 expression in cells is reduced to cells and in cells is of is reduced in cell lines this is with requirement for caveolae formation (7Hill M.M. Bastiani M. Luetterforst R. Kirkham M. Kirkham A. Nixon S.J. Walser P. Abankwa D. Oorschot V.M. Martin S. Hancock J.F. Parton R.G. PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function.Cell. 2008; 132: 113-124Abstract Full Text Full Text PDF PubMed Scopus (514) Google Scholar) but also for stable Cav1 expression L. D. M. D. K. Pilch P.F. of loss of caveolae, and 2008; 8: Full Text Full Text PDF PubMed Scopus Google Scholar). cells caveolae, Cav1 scaffolds and noncaveolar lipid rafts, cells Cav1 scaffolds and noncaveolar lipid rafts and contain noncaveolar lipid rafts This is with the that the functional domains in cells are different from caveolae in cells. show that Cav1 is in in cells with cells of Cav1 in and cell lines to and than with microscopy and This not a cells as the size the of in able to size in these cells particular Cav1 in cells a in of the presence of caveolae and Cav1 Cav1 size in cells This that Cav1 scaffolds are domains than and distinct from caveolae. these cell to distinct caveolar we to mass proteomics to the protein composition of DRMs from these cells L.J. M. proteomics of lipid rafts for signaling PubMed Scopus Google Scholar, A. G. H. R. proteomics of of and transcript release Proteomics. 2010; Full Text Full Text PDF PubMed Scopus Google Scholar, Y.Z. Foster L.J. of proteomics to membrane microdomains.J. Lipid Res. 2009; 50: Full Text Full Text PDF PubMed Scopus Google Scholar). cells were mass with and with of protein from or DRMs were subsequently and by mass for a protein in this that is enriched in the cell DRMs and associated with caveolae a protein as specific to the DRMs of cell or we to a from the for or In a of this proteins specific to DRMs and proteins specific to of than proteins also the of proteins identified in DRMs of protein The the raft protein as as and and the with Cav1 and a and These proteomic data the expression of Cav1 from cells as as the expression of in cells to and enriched in DRMs or membrane rafts of of the cells and identified and in of the were in for and and for Pathways that the proteins enriched in to or cells were to and and and cell signaling this proteins enriched in to or cells and heterotrimeric G-protein and The of heterotrimeric that their in DRMs depends on caveolae formation and that loss of caveolae results in of this class of proteins from membrane rafts. In to the of proteins identified in the data, we used a mass spectrometry to DRMs from and Caveolin-1 embryonic fibroblasts the proteins identified the in the cell and G protein in proteomic proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for proteins the requirement for in a new the distribution of heterotrimeric in and of rafts and caveolae, we the of of with the raft and with with in cells to or cells. also with Cav1 on cells to further expression in the cell lines and to receptor with with raft expression in and distribution in these cells to cells. with expression in cells with in as J.A. Yu J.Z. A. Rasenick M.M. Caveolin-1 and lipid regulate and Pharmacol. 2009; PubMed Scopus Google Scholar). This the expression of heterotrimeric in the proteomic analysis and that caveolae expression promotes recruitment of heterotrimeric to caveolar and noncaveolar raft is with in and cells. and cells were with and with for of in the cell lines are expressing cells were on plasma membrane expression in the presence and of The of cells from independent is for with and cells were with and with for to the cells for with of and are dramatic in the with proteins in the cell rafts and in This that caveolar Cav1 expression proteins to rafts, noncaveolar or Cav1 scaffolds, the with rafts in cells to cells by the proteomics data, of the heterotrimeric identified in the and are enriched in the DRMs and of the proteins enriched in the DRMs were also identified with are in the is Cav1 expression in the Pathways that DRMs are enriched in proteins in and cell as as proteins to and cell we were able to proteins enriched in the proteome and cells that Cav1 scaffolds with a of proteins than caveolae. The dramatic of proteins in in loss of Cav1 scaffolds signaling and and P. G. J. A. Nabi I.R. membrane regulates signaling in tumor Cell Biol. 2007; PubMed Scopus Google Scholar, P. S. Li L. Nabi I.R. Caveolin-1 of of independently of Mol. 2009; PubMed Scopus Google Scholar), that Cav1 regulate raft These are to be by the of a in or with in cells with results in proteins in the DRMs in the we also structures from DRMs of cells and quantitatively the composition of this a and than proteins identified and from independent proteins these Cav1 and with the and PTRF/cavin-1, heterotrimeric and the Cav1-associated proteins, of were also identified to be in the and caveolae proteins identified in in of the proteins in cells with Cav1 and The presence of heterotrimeric G-protein and other signaling proteins supports the role of caveolae formation in the recruitment of these proteins to lipid rafts by Cav1 but also that raft of G proteins independently of Cav1 and caveolae of protein identified to be enriched in rafts to or were with proteins identified to be associated with protein caveolin-1 in the identified to be enriched in rafts to or were with proteins to be to In to of the caveolae proteins identified are of lipid rafts or raft-dependent proteins, we the of the caveolae proteins identified L.J. M. proteomics of lipid rafts for signaling PubMed Scopus Google Scholar). of analyses from cells identified than proteins with and from to than the proteins by of were identified as caveolae proteins from the and are in caveolae Cav1-associated and into the Cav1 with the raft of heterotrimeric in heterotrimeric G-protein identified of their raft other signaling proteins and and and were by with a study Y.Z. Berg K.B. Foster L.J. Mitochondria do not contain lipid rafts, and lipid rafts do not contain mitochondrial proteins.J. Lipid Res. 2009; 50: 988-998Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar) cell biologists for and for that is that multiple distinct of rafts as to a of and is that are to these Cav1 is a regulator of raft domains and we of the distinct of caveolin and caveolae in a of cell lines from wild-type and to caveolar and noncaveolar Cav1 impact on the protein composition of detergent-resistant membranes in cells. of rafts caveolae that of the data to of raft proteins L.J. Lipid raft than detergent-resistant 2007; PubMed Scopus Google Scholar). recent used Cav1−/− cells (7Hill M.M. Bastiani M. Luetterforst R. Kirkham M. Kirkham A. Nixon S.J. Walser P. Abankwa D. Oorschot V.M. Martin S. Hancock J.F. Parton R.G. PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function.Cell. 2008; 132: 113-124Abstract Full Text Full Text PDF PubMed Scopus (514) Google Scholar, A. G. H. R. proteomics of of and transcript release Proteomics. 2010; Full Text Full Text PDF PubMed Scopus Google Scholar) to of the proteins in caveolae but other than Cav1 and members of the cavin family of proteins, of the other proteins to be functional of caveolae. the of caveolar proteins, of signaling proteins in DRMs the role of rafts as signaling and that caveolae and rafts to be enriched for heterotrimeric G protein subunits. In a to the data Cav1 in cells with lipid rafts and in to receptor with J.A. Yu J.Z. A. Rasenick M.M. Caveolin-1 and lipid regulate and Pharmacol. 2009; PubMed Scopus Google Scholar). Our results further that Cav1 expression independently of caveolae, Cav1 scaffolds, is associated with reduced lipid raft of G proteins. Cav1 of and G protein signaling to be associated not with Cav1 expression but also by the expression of caveolae and Cav1 expression of Cav1 and of as in in Cav1 expression. of signaling by expression of Cav1 independently of caveolae Yu J. R. R. expression of caveolin-1 and 2005; PubMed Scopus Google Scholar) that caveolae and Cav1 scaffolds can and independently in the cell to regulate the to expression and on expression of caveolae, Cav1 scaffolds and noncaveolar lipid rafts and their of signaling including but not to G proteins, to be data also that caveolin expression is not the of protein composition of caveolar domains, is in with other that cavin proteins also a role in caveolae formation (7Hill M.M. Bastiani M. Luetterforst R. Kirkham M. Kirkham A. Nixon S.J. Walser P. Abankwa D. Oorschot V.M. Martin S. Hancock J.F. Parton R.G. PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function.Cell. 2008; 132: 113-124Abstract Full Text Full Text PDF PubMed Scopus (514) Google Scholar, K.A. Zajicek H. Li W.P. Peyton M.J. Minna J.D. Hernandez V.J. Luby-Phelps K. Anderson R.G. SRBC/cavin-3 is a caveolin adapter protein that regulates caveolae function.EMBO J. 2009; 28: 1001-1015Crossref PubMed Scopus (158) Google Scholar, 9Bastiani M. Liu L. Hill M.M. Jedrychowski M.P. Nixon S.J. Lo H.P. Abankwa D. Luetterforst R. Fernandez-Rojo M. Breen M.R. Gygi S.P. Vinten J. Walser P.J. North K.N. Hancock J.F. Pilch P.F. Parton R.G. MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes.J. Cell Biol. 2009; 185: 1259-1273Crossref PubMed Scopus (204) Google Scholar, 11Hansen C.G. Bright N.A. Howard G. Nichols B.J. SDPR induces membrane curvature and functions in the formation of caveolae.Nat. Cell Biol. 2009; 11: 807-814Crossref PubMed Scopus (194) Google Scholar). In cells Cav1 is the cell but caveolae do not than as proteins of DRMs as that the caveolae structure a dramatic impact on caveolae and membrane raft This is with that the Cav1 scaffolds the membrane of these cells as domains than caveolae in wild-type cells. Cav1 to of Cav1 caveolae to contain Cav1 S. Parton R.G. J. A. a membrane protein of the caveolar in and in Biol. PubMed Scopus Google Scholar, L. M. and of 2005; PubMed Scopus Google Scholar). we the size of Cav1 scaffolds, the and reduced size of Cav1 in cells caveolae that Cav1 scaffolds to Cav1 that subsequently to form caveolae. The that Cav1 scaffolds the raft proteome to a than caveolae that recruitment to caveolae on Cav1 with proteins and of raft Our data to class of rafts, caveolae, from the in DRMs and the of distinct Cav1-associated the of proteins enriched in Cav1 and the by or cells do not that the proteins that with Cav1 but that are not by caveolae a of Cav1 domains distinct from caveolae. the the of structures we to membranes and Cav1 and proteins this the composition of structures or a we that can be to of the membranes from cells. is used and to and other we that the presence of and the associated in Using a of cell with varying caveolae as as microscopy and microscopy, we show that caveolae and Cav1 scaffolds in size and impact on the protein composition of lipid raft with noncaveolar raft domains, these functionally distinct of lipid rafts. raft protein composition in Cav1 expressing cells argues that Cav1 and to form caveolae impact on raft composition and roles for caveolae. the other members of for are to with to a and with of the Parton for the from for and for with with

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