Protein Kinase C Activators Inhibit Receptor-Mediated Potocytosis by Preventing Internalization of Caveolae

• Published in: The Journal of cell biology Vol. 124; no. 3; pp. 307 - 313
• Main Authors: Smart, Eric J., Foster, David C., Ying, Yun-Shu, Kamen, Barton A., Richard G. W. Anderson
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.02.1994; The Rockefeller University Press
• Subjects: 3T3 cells; Animals; Biological and medical sciences; Carrier Proteins - metabolism; Caveolae; Cell Line; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Cell membranes; Cell physiology; Cells; Cellular biology; Endocytosis; Endocytosis - drug effects; Enzyme Activation; Folate Receptors, GPI-Anchored; Folic Acid - metabolism; Fundamental and applied biological sciences. Psychology; Haplorhini; Internalization; K562 cells; Ligands; Microscopy, Electron; Molecular and cellular biology; Molecules; Protein Kinase C - metabolism; Proteins; Receptors; Receptors, Cell Surface; Tetradecanoylphorbol Acetate - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Tetrahydrofolates - metabolism; Vertebrata; Endocytosis; Protein kinase C; Mammalia; Enzyme; Activator; Monkey; Primates; Inhibition; Biological receptor
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.124.3.307

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.