PROTEIN-KINASE-C ACTIVATORS INHIBIT RECEPTOR-MEDIATED POTOCYTOSIS BY PREVENTING INTERNALIZATION OF CAVEOLAE

Potocytosis is an endocytic pathway that utilizes glycosylphosphatidyl inositol-anchored membrane proteins and caveolae to concentrate and in ternalize small molecules. We now report that activators of protein ki nase C are potent inhibitors of potocytosis. Activators such as phorbo l-12-myristate-13-acetate (PMA) inhibit the internalization of recepto rs for 5-methyltetrahydrofolate but allow the internal receptor pool t o return to the cell surface. PMA does not affect the clustering of th e folate receptor but instead markedly reduces the number of caveolae. Exposure to PMA totally blocks the intracellular accumulation of 5-me thyltetrahydrofolate without affecting receptor-independent uptake or the formation of polyglutamylated species of 5-methyltetrahydrofolate in the cytoplasm. These data suggest that PMA inhibits uptake by inact ivating caveolae internalization.