Protein kinase C regulates endocytosis and recycling of E-cadherin

• Published in: American Journal of Physiology: Cell Physiology Vol. 283; no. 2; pp. C489 - C499
• Main Authors: Le, Tam Luan, Joseph, Shannon R, Yap, Alpha S, Stow, Jennifer L
• Format: Journal Article
• Language: English
• Published: United States 01.08.2002
• Subjects: Actins - metabolism; Adherens Junctions - physiology; Animals; Cadherins - drug effects; Cadherins - metabolism; Cell Adhesion - physiology; Cell Line - drug effects; Cell Membrane - metabolism; Dogs; Endocytosis - drug effects; Endocytosis - physiology; Endosomes - metabolism; Enzyme Inhibitors - pharmacology; Indoles - pharmacology; Maleimides - pharmacology; Polymers - metabolism; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - physiology; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00566.2001

1  Institute for Molecular Bioscience, 2  Department of Biochemistry, and 3  Department of Physiology and Pharmacology, University of Queensland, Brisbane 4072, Queensland, Australia E-cadherin is a major component of adherens junctions in epithelial cells. We showed previously that a pool of cell surface E-cadherin is constitutively internalized and recycled back to the surface. In the present study, we investigated the potential role of protein kinase C (PKC) in regulating the trafficking of surface E-cadherin in Madin-Darby canine kidney cells. Using surface biotinylation and immunofluorescence, we found that treatment of cells with phorbol esters increased the rate of endocytosis of E-cadherin, resulting in accumulation of E-cadherin in apically localized early or recycling endosomes. The recycling of E-cadherin back to the surface was also decreased in the presence of phorbol esters. Phorbol ester-induced endocytosis of E-cadherin was blocked by specific inhibitors, implicating novel PKC isozymes, such as PKC- in this pathway. PKC activation led to changes in the actin cytoskeleton facilitating E-cadherin endocytosis. Depolymerization of actin increased endocytosis of E-cadherin, whereas the PKC-induced uptake of E-cadherin was blocked by the actin stabilizer jasplakinolide. Our findings show that PKC regulates vital steps of E-cadherin trafficking, its endocytosis, and its recycling. trafficking; cell-cell adhesion; actin