Caveolin and cholesterol in lipid transport and signaling

Abstract

Caveolae are free cholesterol-rich invaginated microdomains of the cell surface characterized by the presence of one or more structural proteins (caveolins). The cholesterol-binding capacity of caveolin plays a key role in the organization of signaling complexes within caveolae. Caveolae are particularly rich in multiprotein signaling complexes containing protein growth factor receptors or integrins. Immunoprecipitation of caveolins from cells labeled with 3H free cholesterol (FC) allows proteins and lipids present in caveolae to be identified at intervals following the initiation of signal transduction. Signaling was found to be associated with transient loss of caveolin-associated FC, stimulation of FC efflux, and phosphorylation of caveolin at a sensitive tyrosine residue. FC within caveolae is labile and responsive to changes in the local composition of signaling complexes. In view of the extended residence of caveolae at the cell surface, these data imply that caveolae take part in an FC cycle initiated by the binding of ligand to its transmembrane kinase. Regulated loss of FC from caveolae is followed by a recovery phase when FC content is restored. These changes form an essential part of signal transduction from the cell surface for caveolae-associated signaling complexes.