Roles of aberrant hemichannel activities due to mutant connexin26 in the pathogenesis of KID syndrome

Scientific Reports
T TakiM Akiyama

Abstract

Germline missense mutations in GJB2 encoding connexin (Cx) 26 have been found in keratitis, ichthyosis and deafness (KID) syndrome. We explored the effects of three mouse Cx26 mutants (Cx26-G12R, -G45E and -D50N) corresponding to KID syndrome-causative human mutants on hemichannel activities leading to cell death and the expression of immune response-associated genes. We analyzed the 3D images of cells expressing wild-type (WT) or mutant Cx26 molecules to demonstrate clearly the intracellular localization of Cx26 mutants and hemichannel formation. High extracellular Ca2+ conditions lead to the closure of gap junction hemichannels in Cx26-G12R or Cx26-G45E expressing cells, resulting in prohibition of the Cx26 mutant-induced cell death. Fluorescent dye uptake assays revealed that cells with Cx26-D50N had aberrantly high hemichannel activities, which were abolished by a hemichannel blocker, carbenoxolone and 18α-Glycyrrhetinic acid. These results further support the idea that abnormal hemichannel activities play important roles in the pathogenesis of KID syndrome. Furthermore, we revealed that the expressions of IL15, CCL5, IL1A, IL23R and TLR5 are down-regulated in keratinocytes expressing Cx26-D50N, suggesting that immune defic...Continue Reading

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Citations

Sep 13, 2019·Stomatologii︠a︡·M V KorolenkovaA A Poberezhnaya
Jul 8, 2020·International Journal of Molecular Sciences·María F Rozas-VillanuevaMauricio A Retamal
Mar 18, 2021·International Journal of Dermatology·Min Moon TangZacharias Aloysius Dwi Pramano
Apr 4, 2021·International Journal of Molecular Sciences·Rasheed A BaileyI Martha Skerrett
Aug 26, 2021·Trends in Cell Biology·Dale W Laird, Paul D Lampe

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Methods Mentioned

BETA
transfection
PCR
PCRs

Software Mentioned

DAVID Bioinformatics Resources
ImageJ
Affymetrix Transcriptome Analysis Console

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