title: Post-translational integration and oligomerization of connexin 26 in plasma membranes and evidence of formation of membrane pores: implications for the assembly of gap junctions.
abstract: Gap-junction channels provide a widespread intercellular signalling mechanism. They are constructed of a family of connexin membrane proteins that thread across the membrane four times and oligomerize to generate hexameric gap-junction hemichannels. Using an in vitro cell-free transcription/translation system, we demonstrate that connexin (Cx) 26, one of the smallest connexins, is integrated directly in a post-translational manner into plasma membranes. Protein-cleavage studies of Cx26 integrated into plasma membranes indicate a similar native transmembrane topography to that of Cx26 integrated co-translationally into microsomes. Cx26 integrated post-translationally into plasma membranes oligomerizes and, when incorporated into liposomes, provides permeability to ascorbic acid, suggesting that gap-junction hemichannels are generated. The results provide the basis of a novel alternative mechanism for spontaneous assembly in plasma membranes of Cx26 gap-junction hemichannels that occurs independently of the conventional biogenesis of gap junctions involving connexin trafficking and oligomerization via membrane components of the secretory pathway.
authors: Department of Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, Wales, U.K.
authors: Shoeb
authors: S
authors: Ahmad
authors: W Howard
authors: WH
authors: Evans
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002474:Cell-Free System; D000072259:Connexin 26; D017630:Connexins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D017629:Gap Junctions / Q000378:metabolism*; D006168:Guinea Pigs; D008081:Liposomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: D017630:Connexins; D008081:Liposomes; D000072259:Connexin 26