title: Caveolin forms a hetero-oligomeric protein complex that interacts with an apical GPI-linked protein: implications for the biogenesis of caveolae.
abstract: Glycosyl-phosphatidylinositol (GPI)-linked proteins are transported to the apical surface of epithelial cells where they undergo cholesterol-dependent clustering in membrane micro-invaginations, termed caveolae or plasmalemmal vesicles. However, the sorting machinery responsible for this caveolar-clustering mechanism remains unknown. Using transfected MDCK cells as a model system, we have identified a complex of cell surface molecules (80, 50, 40, 22-24, and 14 kD) that interact in a pH- and cholesterol-dependent fashion with an apical recombinant GPI-linked protein. A major component of this hetero-oligomeric protein complex is caveolin, a type II transmembrane protein. As this hetero-oligomeric caveolin complex is detectable almost immediately after caveolin synthesis, our results suggest that caveolae may assemble intracellularly during transport to the cell surface. As such, our studies have implications for understanding both the intracellular biogenesis of caveolae and their subsequent interactions with GPI-linked proteins in epithelia and other cell types.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
authors.forename: M P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Z L
authors.initials: ZL
authors.lastname: Tang
authors.forename: M
authors.initials: M
authors.lastname: Sargiacomo
mesh_terms: D000818:Animals; D051242:Caveolin 1; D022461:Caveolins; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D004848:Epithelium / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D015151:Immunoblotting; D007668:Kidney; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008970:Molecular Weight; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D022461:Caveolins; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D011994:Recombinant Proteins