The M34A mutant of Connexin26 reveals active conductance states in pore-suspending membranes

J Struct Biol. 2009 Oct;168(1):168-76. doi: 10.1016/j.jsb.2009.02.004. Epub 2009 Feb 21.

Abstract

Connexin26 (Cx26) is a member of the connexin family, the building blocks for gap junction intercellular channels. These dodecameric assemblies are involved in gap junction-mediated cell-cell communication allowing the passage of ions and small molecules between two neighboring cells. Mutations in Cx26 lead to the disruption of gap junction-mediated intercellular communication with consequences such as hearing loss and skin disorders. We show here that a mutant of Cx26, M34A, forms an active hemichannel in lipid bilayer experiments. A comparison with the Cx26 wild-type is presented. Two different techniques using micro/nano-structured substrates for the formation of pore-suspending lipid membranes are used. We reconstituted the Cx26 wild-type and Cx26M34A into artificial lipid bilayers and observed single channel activity for each technique, with conductance levels of around 35, 70 and 165 pS for the wild-type. The conductance levels of Cx26M34A were found at around 45 and 70 pS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Connexin 26
  • Connexins / chemistry*
  • Connexins / genetics
  • Connexins / metabolism*
  • Gap Junctions / chemistry*
  • Gap Junctions / metabolism*
  • Humans
  • Lipid Bilayers / chemistry*
  • Lipid Bilayers / metabolism*
  • Mutation
  • Rats

Substances

  • Connexins
  • GJB2 protein, human
  • Lipid Bilayers
  • Connexin 26