title: Muscle-specific interaction of caveolin isoforms: differential complex formation between caveolins in fibroblastic vs. muscle cells.
abstract: It is generally well accepted that caveolin-3 expression is muscle specific, whereas caveolin-1 and -2 are coexpressed in a variety of cell types, including adipocytes, endothelial cells, epithelial cells, and fibroblasts. Caveolin-1 and -2 are known to form functional hetero-oligomeric complexes in cells where they are coexpressed, whereas caveolin-3 forms homo-oligomeric high molecular mass complexes. Although caveolin-2 might be expected to interact in a similar manner with caveolin-3, most studies indicate that this is not the case. However, this view has recently been challenged as it has been demonstrated that caveolin-2 and -3 are coexpressed in primary cultures of cardiac myocytes, where these two proteins can be coimmunoprecipitated. Thus it remains controversial whether caveolin-2 interacts with caveolin-3. Here, we directly address the issue of caveolin isoform protein-protein interactions by means of three distinct molecular genetic approaches. First, using caveolin-1-deficient mouse embryonic fibroblasts, in which we have stably expressed caveolin-1, -2, or -3, we find that caveolin-1 interacts with caveolin-2 in this setting, whereas caveolin-3 does not, in agreement with most published observations. Next, we used a transfected L6 myoblast cell system expressing all three caveolin proteins. Surprisingly, we found that caveolin-1, -2, and -3 all coimmunoprecipitate in this cell type, suggesting that this interaction is muscle cell specific. Similar results were obtained when the skeletal muscle of caveolin-1 transgenic animals was analyzed for caveolin-1 and caveolin-3 coimmunoprecipitation. Thus we conclude that all three caveolins can interact to form a discrete hetero-oligomeric complex, but that such complex formation is clearly muscle specific.
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, and The Albert Einstein Cancer Center, 1300 Morris Park Ave., Bronx, NY 10461, USA.
authors.forename: Franco
authors.initials: F
authors.lastname: Capozza
authors.forename: Alex W
authors.initials: AW
authors.lastname: Cohen
authors.forename: Michelle W-C
authors.initials: MW
authors.lastname: Cheung
authors.forename: Federica
authors.initials: F
authors.lastname: Sotgia
authors.forename: William
authors.initials: W
authors.lastname: Schubert
authors.forename: Michela
authors.initials: M
authors.lastname: Battista
authors.forename: Hyangkyu
authors.initials: H
authors.lastname: Lee
authors.forename: Philippe G
authors.initials: PG
authors.lastname: Frank
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
mesh_terms: D000818:Animals; D021941:Caveolae / Q000737:chemistry / Q000378:metabolism; D022461:Caveolins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003902:Detergents / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D046911:Macromolecular Substances; D051379:Mice; D018345:Mice, Knockout; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism* / Q000648:ultrastructure; D017830:Octoxynol / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism
chemical_list: D022461:Caveolins; D003902:Detergents; D046911:Macromolecular Substances; D020033:Protein Isoforms; D017830:Octoxynol