title: The protein phosphatase 2A regulatory subunit Ppp2r2a is required for Connexin-43 dephosphorlyation during epidermal barrier acquisition.
abstract: Epidermal barrier acquisition during late mammalian development is a prerequisite for terrestrial existence. Over a 24-h period, the epidermis goes from being a barrier-deficient, dye permeable epithelium to a barrier-competent epithelium. We have previously shown that Akt signalling is necessary for barrier acquisition in the mouse and that the protein phosphatase 2A regulatory subunit Ppp2r2a causes barrier acquisition by dephosphorylation of cJun. Here, we demonstrate that there is transient interaction between the gap junction protein Connexin 43 (Cx43) and Zonula occludins-1 (Zo-1) during epidermal barrier acquisition. Ppp2r2a knockdown prevented plasma membrane co-localisation and interaction between the two proteins. Ppp2r2a knockdown also increased phosphorylation at Serine 368 of Connexin 43. Cx43 phosphorlyation at Serine368 occurred just prior to the interaction between Connexin 43 and Zo-1. We therefore propose a model in which Ppp2r2a is required both for the initial interaction between Zo-1 and Cx43 and the consequent dephosphorylation of Connexin 43, preventing interaction of Zo-1 and allowing Zo-1 to initiate tight junction formation and barrier acquisition.
authors.affiliation: Immunobiology and Dermatology, UCL Institute of Child Health, London, UK; Prostate Cancer Research Group, Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway.
authors.forename: Lisa
authors.initials: L
authors.lastname: Gerner
authors.forename: Gehad
authors.initials: G
authors.lastname: Youssef
authors.forename: Ryan F L
authors.initials: RF
authors.lastname: O'Shaughnessy
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D018031:Connexin 43 / Q000737:chemistry*; D017630:Connexins / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000502:physiology*; D017434:Protein Structure, Tertiary; D051381:Rats; D015398:Signal Transduction; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D018031:Connexin 43; D017630:Connexins; C543076:GJA1 protein, mouse; C580592:Gja1 protein, rat; D008565:Membrane Proteins; C569043:Tjp1 protein, mouse; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D048031:JNK Mitogen-Activated Protein Kinases; C581986:Ppp2r2a protein, mouse; D054648:Protein Phosphatase 2
keywords: epidermal barrier; gap junction; tight junction