The detergent resistance of Connexin43 is lost upon TPA or EGF treatment and is an early step in gap junction endocytosis.
Gap junctions are plasma membrane domains containing channels that directly connect the cytosols of neighbouring cells. Gap junction channels are made of a family of transmembrane proteins called connexins, of which the best studied is Connexin43 (Cx43). MAP kinase-induced phosphorylation of Cx43 has previously been shown to cause inhibition of gap junction channel permeability and increased Cx43 endocytosis. As Cx43 assembles into gap junction plaques, Cx43 acquires detergent resistance. Here we report that the detergent resistance is lost after activation of MAP kinase. Treatment of IAR20 rat liver epithelial cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) or epidermal growth factor (EGF) caused a rapid increase in the solubility of Cx43 in Triton X-100. This process was mediated by MAP kinase and was initiated at the plasma membrane. The data suggest that loss of the detergent resistance of Cx43 is an early step in TPA- and EGF-induced endocytosis of gap junctions.
Sirnes
Solveig
S
Department of Cancer Prevention, The Norwegian Radium Hospital, Rikshospitalet, Montebello, Oslo, Norway.
Leithe
Edward
E
Rivedal
Edgar
E
D000818:Animals; D002460:Cell Line; D018031:Connexin 43 / Q000737:chemistry* / Q000378:metabolism*; D004705:Endocytosis; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D017629:Gap Junctions / Q000201:enzymology / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017830:Octoxynol / Q000737:chemistry; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D012995:Solubility; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018031:Connexin 43; D004815:Epidermal Growth Factor; D017830:Octoxynol; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate