Incorporation of connexins into plasma membranes and gap junctions.
Gap junctions are polymeric assemblies of aligned pairs of interacting hexameric connexon hemichannel units facilitating direct intercellular communication. The principal process leading to assembly of gap junctions involves the cotranslational insertion of connexin (Cx) proteins into the endoplasmic reticulum, followed by their rapid oligomeric association into homo- or heteromeric connexons that are trafficked via the Golgi apparatus to the plasma membrane. Oligomerisation is a high-fidelity process that determines connexon channel stoichiometry and conductance characteristics. A large number of mutations in Cx26 and Cx32 detected in genetic diseases have emphasised the requirement for precise oligomerisation of connexins into hexameric connexons that traffic to the plasma membrane. Mutations in Cx43 are rare, and in the cardiovascular system, where it is the dominant connexin, disease changes are linked to its abundance and to gap junction remodelling. Connexins with short carboxyl tails may also be post-translationally inserted as oligomeric channels directly into plasma membranes. This mechanism of channel assembly is highly dependent on microtubule integrity and may allow cells to rapidly modulate gap junctional cross talk.
Martin
Patricia E M
PE
Department of Medical Biochemistry and Immunology and Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK. patricia.martin@gcal.ac.uk
Evans
W Howard
WH
D001692:Biological Transport; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D000072259:Connexin 26; D017630:Connexins / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism*
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26