Functional analysis of selective interactions among rodent connexins

Mol Biol Cell. 1995 Apr;6(4):459-70. doi: 10.1091/mbc.6.4.459.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Communication / genetics
  • Cell Communication / physiology*
  • Connexin 26
  • Connexins / genetics
  • Connexins / metabolism*
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Female
  • Gene Expression Regulation
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism
  • Oocytes
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rodentia
  • Xenopus laevis


  • Connexins
  • Eye Proteins
  • GJB2 protein, Xenopus
  • Ion Channels
  • Membrane Glycoproteins
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • connexin 32
  • connexin 46
  • connexin 50
  • Connexin 26