Protein kinase C regulates endocytosis and recycling of E-cadherin.
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-epsilon 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.
Le
Tam Luan
TL
Institute for Molecular Bioscience, Department of Biochemistry, University of Queensland, Brisbane 4072, Queensland, Australia.
Joseph
Shannon R
SR
Yap
Alpha S
AS
Stow
Jennifer L
JL
D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000502:physiology; D000818:Animals; D015820:Cadherins / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D011108:Polymers / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000199:Actins; D015820:Cadherins; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D011108:Polymers; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate