Properties of human connexin 31, which is implicated in hereditary dermatological disease and deafness

Abstract

The connexins are a family of at least 20 homologous proteins in humans that form aqueous channels connecting the interiors of coupled cells and mediating electrical and chemical communication. Mutations in the gene for human connexin 31 (hCx31) are associated with disorders of the skin and auditory system. Alterations in functional properties of Cx31 junctions are likely to play a role in these diseases; nonetheless, little is known about the properties of the wild-type channels. Here we show that hCx31 channels, like other connexin channels, are gated by voltage and close at low pH and when exposed to long-chain alkanols. Singlechannel conductance of the fully open channel is Ϸ85 pS, and it is permeable to Lucifer yellow, Alexa Fluor 350 , ethidium bromide, and DAPI, which have valences of ؊2, ؊1, ؉1, and ؉2, respectively. In contrast to what has been reported for mouse Cx31, hCx31 appears to form functional heterotypic channels with all four connexins tested, Cx26, Cx30, Cx32, and Cx45. These findings provide an important first step in evaluating the pathogenesis of inherited human diseases associated with mutations in the gene for Cx31.electrical coupling ͉ erythrokeratodermia variabilis ͉ gap junction ͉ intercellular communication

Two Distinct Heterotypic Channels Mediate Gap Junction Coupling between Astrocyte and Oligodendrocyte Connexins

“…The human Cx30, Cx32, and Cx47 clones were generated as described previously (Abrams et al, 2006;Orthmann-Murphy et al, 2007). The human Cx43 open reading frame was generated similarly to the Cx47 clone, using primers based on the GenBank accession number NM_000165 DNA sequence, by reverse transcription-PCR (SuperScript II; Invitrogen, Carlsbad, CA).…”

“…Dye-transfer studies were performed as described previously (Abrams et al, 2006). Briefly, intercellular dye transfer was measured by monitoring fluorescence intensity in both cells of a pair after loading one cell with dye via patch pipette in whole-cell configuration.…”

Gap Junctions

“…More than half of all profound hereditary deafness results from mutations in Cx26, which are often syndromic and involve skin disorders (Kelsell et al 1997;Denoyelle et al 1997). Similarly, although usually less severe, disorders of the skin and the auditory system accompany mutations in Cx31 and Cx30 (Common et al 2002;Abrams et al 2006;Yang et al 2007;Apps et al 2007;Yum et al 2007). Familial cataracts are commonly associated with mutations in either Cx46 or Cx50, whose expression is largely restricted to the ocular lens (Gong et al 2007;Richard 2005;van Steensel 2004;Vreeburg et al 2007;Mese et al 2007).…”

Modulation of metabolic communication through gap junction channels by transjunctional voltage; synergistic and antagonistic effects of gating and ionophoresis

“…The normalized g j – V j dependence is strongly asymmetric with a peak of g j at V j ≈−25 mV. The reduction of g j at positive V j s is caused by the closure of Cx45 aHCs that gate at relative negativity on their cytoplasmic side [9], whereas the reduction in g j for negative V j s results from closure of Cx31 aHCs that also gate at relative negativity but are less V j sensitive than Cx45 aHC [61]. Similar V j -gating asymmetry was reported for mCx30.2/Cx45 [15], Cx40/Cx45 [10], Cx43/Cx45 [9] and Cx57/Cx45 [62] GJs and observed in Cx36/Cx45 and Cx47/Cx45 GJs (unpublished data, F.F.B.…”