Identification of a proline residue as a transduction element involved in voltage gating of gap junctions.
Gap junction channels are structurally distinct from other ion channels in that they comprise two hemichannels which interact head-to-head to form an aqueous channel between cells. Intercellular voltage differences together with increased intracellular concentrations of H+ and Ca2+ cause closure of these normally patent channels. The relative sensitivity to voltage varies with the subunit (connexin) composition of the channels. The third of four transmembrane-spanning regions (M3) in connexins has been proposed to form the channel lining, and a global 'tilting' of the hemichannel subunits has been correlated with channel closure. But specific components involved in transduction of channel gating events have not been identified in either gap junctions or other ion channel classes (however, see model in ref. 5). We have examined a strictly conserved proline centrally located in M2 of connexin proteins. Mutation of this proline (Pro 87) in connexin 26 causes a reversal in the voltage-gating response when the mutant hemichannel is paired with wild-type connexin 26 in the Xenopus oocyte system. This suggests that the unique properties associated with this residue are critical to the transduction of voltage gating in these channels.
Suchyna
T M
TM
Department of Biological Sciences, State University of New York at Buffalo 14260.
Xu
L X
LX
Gao
F
F
Fourtner
C R
CR
Nicholson
B J
BJ
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D003001:Cloning, Molecular; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000502:physiology*; D004594:Electrophysiology; D017629:Gap Junctions / Q000502:physiology*; D005914:Globins / Q000235:genetics; D015640:Ion Channel Gating / Q000502:physiology*; D008969:Molecular Sequence Data; D009865:Oocytes; D011392:Proline / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014981:Xenopus; D000097002:Gap Junction beta-1 Protein
D000072259:Connexin 26; D017630:Connexins; D005914:Globins; D011392:Proline; D011993:Recombinant Fusion Proteins; D000097002:Gap Junction beta-1 Protein; C000607045:GJB2 protein, Xenopus