Protein kinase C activators inhibit receptor-mediated potocytosis by preventing internalization of caveolae.
Potocytosis is an endocytic pathway that utilizes glycosylphosphatidylinositol-anchored membrane proteins and caveolae to concentrate and internalize small molecules. We now report that activators of protein kinase C are potent inhibitors of potocytosis. Activators such as phorbol-12-myristate-13-acetate (PMA) inhibit the internalization of receptors for 5-methyltetrahydrofolate but allow the internal receptor pool to return to the cell surface. PMA does not affect the clustering of the folate receptor but instead markedly reduces the number of caveolae. Exposure to PMA totally blocks the intracellular accumulation of 5-methyltetrahydrofolate 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 inactivating caveolae internalization.
Smart
E J
EJ
Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, Dallas 75235.
Foster
D C
DC
Ying
Y S
YS
Kamen
B A
BA
Anderson
R G
RG
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure*; D004705:Endocytosis / Q000187:drug effects*; D004789:Enzyme Activation; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D000882:Haplorhini; D008854:Microscopy, Electron; D011493:Protein Kinase C / Q000378:metabolism*; D011956:Receptors, Cell Surface; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology*; D013763:Tetrahydrofolates / Q000378:metabolism*
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D013763:Tetrahydrofolates; D005492:Folic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C005984:5-methyltetrahydrofolate