Caveolin-1 interacts with the chaperone complex TCP-1 and modulates its protein folding activity

Cell Mol Life Sci. 2006 Apr;63(7-8):939-48. doi: 10.1007/s00018-005-5551-z.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Caveolin 1 / metabolism*
  • Cell Line
  • Chaperonin Containing TCP-1
  • Chaperonins / drug effects
  • Chaperonins / metabolism*
  • HT29 Cells
  • Humans
  • Insulin / pharmacology
  • Molecular Sequence Data
  • Multiprotein Complexes / metabolism
  • Phosphorylation
  • Protein Folding*
  • Signal Transduction

Substances

  • Caveolin 1
  • Insulin
  • Multiprotein Complexes
  • Chaperonin Containing TCP-1
  • Chaperonins