A deafness-associated mutant human connexin 26 improves the epithelial barrier in vitro.
A large proportion of recessive nonsyndromic hearing loss is due to mutations in the GJB2 gene encoding connexin 26 (Cx26), a component of a gap junction. Within different ethnic groups there are specific common recessive mutations, each with a relatively high carrier frequency, suggesting the possibility of heterozygous advantage. Carriers of the R143W GJB2 allele, the most prevalent in the African population, present with a thicker epidermis than noncarriers. In this study, we show that (R143W)Cx26-expressing keratinocytes form a significantly thicker epidermis in an organotypic coculture skin model. In addition, we show increased migration of cells expressing (R143W)Cx26 compared to (WT)Cx26-overexpressing cells. We also demonstrate that cells expressing (R143W)Cx26 are significantly less susceptible to cellular invasion by the enteric pathogen Shigella flexneri than (WT)Cx26-expressing cells. These in vitro studies suggest an advantageous effect of (R143W)Cx26 in epithelial cells.
Man
Y K Stella
YK
Centre for Cutaneous Research, Institute of Cell and Molecular Science, Queen Mary University of London, 4 Newark Street, Whitechapel, London, UK.
Trolove
Caroline
C
Tattersall
Daniel
D
Thomas
Anna C
AC
Papakonstantinopoulou
Annie
A
Patel
Drashnika
D
Scott
Claire
C
Chong
Jiehan
J
Jagger
Daniel J
DJ
O'Toole
Edel A
EA
Navsaria
Harshad
H
Curtis
Michael A
MA
Kelsell
David P
DP
D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells / Q000382:microbiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009924:Organ Culture Techniques; D010957:Plasmids; D012763:Shigella flexneri / Q000472:pathogenicity
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26