Connexin phosphorylation as a regulatory event linked to gap junction internalization and degradation.
Gap junction proteins, connexins, are dynamic polytopic membrane proteins that exhibit unprecedented short half-lives of only a few hours. Consequently, it is well accepted that in addition to channel gating, gap junctional intercellular communication is regulated by connexin biosynthesis, transport and assembly as well as the formation and removal of gap junctions from the cell surface. At least nine members of the 20-member connexin family are known to be phosphorylated en route or during their assembly into gap junctions. For some connexins, notably Cx43, evidence exists that phosphorylation may trigger its internalization and degradation. In recent years it has become apparent that the mechanisms underlying the regulation of connexin turnover are quite complex with the identification of many connexin binding molecules, a multiplicity of protein kinases that phosphorylate connexins and the involvement of both lysosomal and proteasomal pathways in degrading connexins. This paper will review the evidence that connexin phosphorylation regulates, stimulates or triggers gap junction disassembly, internalization and degradation.
Laird
Dale W
DW
Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A-5C1. dale.laird@fmd.uwo.ca
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000502:physiology; D005136:Eye Proteins / Q000378:metabolism; D017629:Gap Junctions / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D010766:Phosphorylation
D018031:Connexin 43; D017630:Connexins; D005136:Eye Proteins; C078866:connexin 56; D004815:Epidermal Growth Factor; D016203:CDC2 Protein Kinase