title: Functional studies of human skin disease- and deafness-associated connexin 30 mutations.
abstract: Connexin 30 (Cx30) is a component of the gap junction complex. Dominant and recessive mutations in the GJB6 gene encoding Cx30 are associated with a variety of human inherited diseases primarily affecting the epidermis, hair, nail, and/or the inner ear. The underlying mechanism of disease associated with different GJB6 mutations such as the disruption of gap junction mediated intercellular communication is unknown. Towards understanding these disease mechanisms, transfection studies were performed in a keratinocyte cell line and in HeLa cells using EGFP tagged wildtype Cx30 and mutant Cx30 constructs harbouring dominant disease-associated GJB6 mutations. For all three of the skin disease-associated Cx30 mutations investigated, impaired trafficking of the protein to the plasma membrane was observed thus preventing the formation of functional Cx30 gap junctions. In contrast, the deafness-associated mutation T5M-Cx30/EGFP trafficked to the membrane but defective channel activity was observed following dye transfer studies.
authors.affiliation: Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, Whitechapel, UK.
authors.forename: John E A
authors.initials: JE
authors.lastname: Common
authors.forename: David
authors.initials: D
authors.lastname: Becker
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Di
authors.forename: Irene M
authors.initials: IM
authors.lastname: Leigh
authors.forename: Edel A
authors.initials: EA
authors.lastname: O'Toole
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsell
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics; D003638:Deafness / Q000235:genetics* / Q000378:metabolism; D004476:Ectodermal Dysplasia / Q000235:genetics / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism; D005799:Genes, Dominant; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012871:Skin Diseases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000075302:Connexin 30; D017630:Connexins; C491020:GJB6 protein, human; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D004247:DNA