Characterization of a Cytosolic Heat-shock Protein-Caveolin Chaperone Complex

• Published in: The Journal of biological chemistry Vol. 273; no. 11; pp. 6525 - 6532
• Main Authors: Uittenbogaard, Annette, Ying, Yun-shu, Smart, Eric J.
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 01.03.1998
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.11.6525

Caveolin is a 22-kDa protein that appears to play a critical role in regulating the cholesterol concentration of caveolae. Even though caveolin is thought to be a membrane protein, several reports suggest that this peculiar protein can traffic independently of membrane vesicles. We now present evidence that a cytosolic pool of caveolin is part of a heat-shock protein-immunophilin chaperone complex consisting of caveolin, heat-shock protein 56, cyclophilin 40, cyclophilin A, and cholesterol. Treatment of NIH 3T3 cells with 1 μ m cyclosporin A or 100 n m rapamycin disrupted the putative transport complex and prevented rapid (10–20 min) transport of cholesterol to caveolae. The lymphoid cell line, L1210-JF, does not express caveolin, does not form an immunophilin-caveolin complex, and does not transport newly synthesized cholesterol to caveolae. Transfection of caveolin cDNA into L1210-JF cells allowed the assembly of a transport complex identical to that found in NIH 3T3 cells. In addition, newly synthesized cholesterol in transfected cells was rapidly (10–20 min) and specifically transported to caveolae. These data strongly suggest that a caveolin-chaperone complex is a mechanism by which newly synthesized cholesterol is transported from the endoplasmic reticulum through the cytoplasm to caveolae.