Tissue-specific effects of wild-type and mutant connexin 31: a role in neurite outgrowth.
Channels formed by connexins (Cx), the major protein subunits of gap junctions, allow passage of ions and molecular messengers between cells to provide a mechanism of synchronized cellular response. Twenty human Cx isoforms have been identified and mutations in the gene GJB3 encoding the 31 kDa isoform, Cx31, can cause dominant or recessive skin disease, dominant or recessive deafness or dominant neuropathy with deafness. Cx31 is expressed in differentiating keratinocytes in skin. Here, we also demonstrate endogenous Cx31 expression in human neuronal cell lines, particularly in differentiated neurones. Exogenous Cx31 expression induced neurite outgrowth in human neuronal cell lines, but not differentiation in primary human keratinocytes. Though neither the neuropathy and hearing loss mutation (66delD)Cx31 nor the skin disease associated mutation (R42P)Cx31 is able to traffic to the plasma membrane, the R42P mutant induced neurite outgrowth to a level equal to wild-type Cx31. In contrast, there was significantly reduced neurite outgrowth after (66delD)Cx31 expression. In addition to indicating a potential disease mechanism for the neuropathy/deafness mutation, this work demonstrates a tissue-specific function for Cx31.
Unsworth
Harriet C
HC
Centre for Cutaneous Research, Queen Mary's School of Medicine and Dentistry, University of London, Whitechapel, E1 4AT, UK.
Aasen
Trond
T
McElwaine
Suzanne
S
Kelsell
David P
DP
D002460:Cell Line; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D046228:Microarray Analysis; D020125:Mutation, Missense / Q000235:genetics*; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology
D017630:Connexins; D020033:Protein Isoforms; C068044:GJB3 protein, human