title: Functional analysis of selective interactions among rodent connexins.
abstract: One consequence of the diversity in gap junction structural proteins is that cells expressing different connexins may come into contact and form intercellular channels that are mixed in connexin content. We have systematically examined the ability of adjacent cells expressing different connexins to communicate, and found that all connexins exhibit specificity in their interactions. Two extreme examples of selectivity were observed. Connexin40 (Cx40) was highly restricted in its ability to make heterotypic channels, functionally interacting with Cx37, but failing to do so when paired with Cx26, Cx32, Cx43, Cx46, and Cx50. In contrast, Cx46 interacted well with all connexins tested except Cx40. To explore the molecular basis of connexin compatibility and voltage gating, we utilized a chimera consisting of Cx32 from the N-terminus to the second transmembrane domain, fused to Cx43 from the middle cytoplasmic loop to the C-terminus. The chimeric connexin behaved like Cx43 with regard to selectivity and like Cx32 with regard to voltage dependence. Taken together, these results demonstrate that the second but not the first extracellular domain affects compatibility, whereas voltage gating is strongly influenced by sequences between the N-terminus and the second transmembrane domain.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: White
authors.forename: D L
authors.initials: DL
authors.lastname: Paul
authors.forename: D A
authors.initials: DA
authors.lastname: Goodenough
authors.forename: R
authors.initials: R
authors.lastname: Bruzzone
mesh_terms: D000818:Animals; D001483:Base Sequence; D002450:Cell Communication / Q000235:genetics / Q000502:physiology*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D009865:Oocytes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012377:Rodentia; D014982:Xenopus laevis; D000097002:Gap Junction beta-1 Protein; D000099264:Connexin 50
chemical_list: D000072259:Connexin 26; D017630:Connexins; D005136:Eye Proteins; D007473:Ion Channels; D008562:Membrane Glycoproteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D000097002:Gap Junction beta-1 Protein; D000099264:Connexin 50; C000607045:GJB2 protein, Xenopus; C082917:GJA3 protein, human