title: Cx30 exhibits unique characteristics including a long half-life when assembled into gap junctions.
abstract: In the present study we investigated the life cycle, trafficking, assembly and cell surface dynamics of a poorly characterized connexin family member, connexin 30 (Cx30; also known as GJB6), which plays a critical role in skin health and hearing. Unexpectedly, Cx30 localization at the cell surface and gap junctional intercellular communication was not affected by prolonged treatments with the endoplasmic reticulum (ER)-Golgi transport inhibitor brefeldin A or the protein synthesis inhibitor cycloheximide, whereas Cx43 (also known as GJA1) was rapidly cleared. Fluorescent recovery after photobleaching revealed that Cx30 plaques were rebuilt from the outer edges in keeping with older channels residing in the inner core of the plaque. Expression of a dominant-negative form of Sar1 GTPase led to the accumulation of Cx30 within the ER, in contrast to a report that Cx30 traffics via a Golgi-independent pathway. Co-expression of Cx30 with Cx43 revealed that these connexins segregate into distinct domains within common gap junction plaques, suggesting that their assembly is governed by different mechanisms. In summary, Cx30 was found to be an unusually stable, long-lived connexin (half-life >12 h), which may underlie its specific role in the epidermis and cochlea.
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A-5C1.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kelly
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A-5C1.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Ear Institute, University College London, London, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Jagger
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A-5C1 Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada N6A-5C1 Dale.Laird@schulich.uwo.ca.
authors.forename: Dale W
authors.initials: DW
authors.lastname: Laird
mesh_terms: D000818:Animals; D000072259:Connexin 26; D000075302:Connexin 30; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D017629:Gap Junctions / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D051381:Rats
chemical_list: D000075302:Connexin 30; D018031:Connexin 43; D017630:Connexins; C491020:GJB6 protein, human; D000072259:Connexin 26
keywords: Connexin; Connexin 30; Cx30; Gap junction; Life cycle; Trafficking