Heteromeric connexin 43/connexin 33 complex endocytosis: a connexin phosphorylation independent mechanism.
The role of gap junctions in proliferation, differentiation and apoptosis has been recently highlighted. Nevertheless, the molecular mechanisms that control these physiological events by acting on gap junction channels are still unknown. We have recently demonstrated that heteromeric gap junction plaques composed by Cx43 and Cx33 are unstable at the cell boundary and are rapidly internalized by endocytosis. In the present study, we analyze the phosphorylation status of Cx43 in homomeric (Cx43/Cx43) and heteromeric (Cx33/Cx43) complexes and their association with the tyrosine kinase c-Src. Our data show that c-Src interaction and P2 phosphorylation of Cx43, which are essential for homomeric Cx43 complex endocytosis, were altered in the heteromeric Cx33/Cx43 complex: lack of association between Cx33 and activated c-Src and disappearance of the P2 phosphorylated Cx43 isoform. The present findings demonstrate that the interaction of Cx33 with Cx43 within a same heteromeric complex may conduce to channel instability through alteration of the phosphorylation status of Cx43 independently of the control of the c-Src kinase. The data described here emphasize a new mechanism of Cx43 internalization Src kinase-independent.
INSERM U895, Université de Nice Sophia Antipolis, Bâtiment Universitaire ARCHIMED, C3M, 151 route Saint-Antoine de Ginestière, BP 2 3194, 06204 Nice cedex 3, France.
Diane
D
Carette
Jérome
J
Gilleron
Dominique
D
Segretain
Georges
G
Pointis
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D018031:Connexin 43 / Q000737:chemistry / Q000378:metabolism*; D017630:Connexins / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017386:Sequence Homology, Amino Acid; D012708:Sertoli Cells / Q000378:metabolism
D018031:Connexin 43; D017630:Connexins; C099106:Gja6 protein, rat