Journal of Membrane Biology

, Volume 218, Issue 1–3, pp 29–37 | Cite as

A Deafness-Associated Mutant Human Connexin 26 Improves the Epithelial Barrier In Vitro

  • Y. K. Stella Man
  • Caroline Trolove
  • Daniel Tattersall
  • Anna C. Thomas
  • Annie Papakonstantinopoulou
  • Drashnika Patel
  • Claire Scott
  • Jiehan Chong
  • Daniel J. Jagger
  • Edel A. O’Toole
  • Harshad Navsaria
  • Michael A. Curtis
  • David P. Kelsell
Article

Abstract

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.

Keywords

Connexin 26 Deafness Epithelial barrier 

Notes

Acknowledgements

This work was funded by the Research Advisory Board of Barts and the London, the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust to D. P. K. We express special thanks to Dr. Jash Vyas for advice and help with the migration assays and Professor Tom MacDonald for the normal human colon and help with interpretation of Cx26 localization.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Y. K. Stella Man
    • 1
  • Caroline Trolove
    • 1
  • Daniel Tattersall
    • 1
  • Anna C. Thomas
    • 1
  • Annie Papakonstantinopoulou
    • 2
  • Drashnika Patel
    • 1
  • Claire Scott
    • 1
  • Jiehan Chong
    • 3
  • Daniel J. Jagger
    • 3
  • Edel A. O’Toole
    • 1
  • Harshad Navsaria
    • 1
  • Michael A. Curtis
    • 2
  • David P. Kelsell
    • 1
  1. 1.Centre for Cutaneous Research, Institute of Cell and Molecular ScienceQueen Mary University of LondonLondonUnited Kingdom
  2. 2.Centre for Infectious Diseases, Institute of Cell and Molecular ScienceQueen Mary University of LondonLondonUnited Kingdom
  3. 3.Centre for Auditory Research, UCL Ear InstituteUniversity College LondonLondonUnited Kingdom

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