HORMONAL-REGULATION OF CAVEOLAE INTERNALIZATION

Caveolae undergo a cyclic transition from a flat segment of membrane t o a vesicle that then returns to the cell surface. Here we present evi dence that this cycle depends on a population of protein kinase C-alph a (PKC-alpha) molecules that reside in the caveolae membrane where the y phosphorylate a 90-kD protein. This cycle can be interrupted by trea tment of the cells with phorbol-12,13-dibutyrate or agents that raise the concentration of diacylglycerol in the cell. Each of these conditi ons displaces PKC-alpha from caveolae, inhibits the phosphorylation of the 90-kD protein, and prevents internalization. Caveolae also contai n a protein phosphatase that dephosphorylates the 90-kD once PKC-alpha is gone, A similar dissociation of PKC-alpha from caveolae and inhibi tion of invagination was observed when cells were treated with histami ne, This effect was blocked by pyrilamine but not cimetidine, indicati ng the involvement of histamine H-1 receptors, These findings suggest that the caveolae internalization cycle is hormonally regulated.