Caveolin-1 interacts with the chaperone complex TCP-1 and modulates its protein folding activity.
We report that caveolin-1, one of the major structural protein of caveolae, interacts with TCP-1, a hetero-oligomeric chaperone complex present in all eukaryotic cells that contributes mainly to the folding of actin and tubulin. The caveolin-TCP-1 interaction entails the first 32 amino acids of the N-terminal segment of caveolin. Our data show that caveolin-1 expression is needed for the induction of TCP-1 actin folding function in response to insulin stimulation. Caveolin-1 phosphorylation at tyrosine residue 14 induces the dissociation of caveolin-1 from TCP-1 and activates actin folding. We show that the mechanism by which caveolin-1 modulates TCP-1 activity is indirect and involves the cytoskeleton linker filamin. Filamin is known to bind caveolin-1 and to function as a negative regulator of insulin-mediated signaling. Our data support the notion that the caveolin-filamin interaction contributes to restore insulin-mediated phosphorylation of caveolin, thus allowing the release of active TCP-1.
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland. doucey@hotmail.com
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D000595:Amino Acid Sequence; D051242:Caveolin 1 / Q000378:metabolism*; D002460:Cell Line; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000187:drug effects / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D010766:Phosphorylation; D017510:Protein Folding; D015398:Signal Transduction
D051242:Caveolin 1; D007328:Insulin; D046912:Multiprotein Complexes; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins