title: CASK (LIN2) interacts with Cx43 in wounded skin and their coexpression affects cell migration.
abstract: Vertebrate gap junctions are composed of proteins from the connexin family. Co-immunoprecipitation, in vitro binding and far western experiments demonstrate that mammalian CASK (also known as LIN2) directly interacts with Cx43. Immunoprecipitation studies indicate that the CASK mainly interacts with the hypophosphorylated form of Cx43. Functional co-regulation of these proteins was found in MDCK cells migrating into a scratch wound, where expression of either protein individually inhibits migration but their coexpression abrogates this inhibitory effect. Immunofluorescence shows colocalization of Cx43 and CASK in mouse brain astrocytes and in response to wounding in human foreskin. During wounding, CASK is mobilized to the plasma membrane where it colocalizes with Cx43 and CADM1 1 hour after skin explant wounding. Together, these studies indicate that CASK interaction with Cx43 occurs relatively early in the connexin life cycle and imply a plasma membrane targeting role for the interaction that apparently affects cellular processes including cellular migration and wound healing.
authors.affiliation: Molecular Diagnostics Program, Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
authors.forename: Lucrecia
authors.initials: L
authors.lastname: Márquez-Rosado
authors.forename: Deepika
authors.initials: D
authors.lastname: Singh
authors.forename: Hector
authors.initials: H
authors.lastname: Rincón-Arano
authors.forename: Joell L
authors.initials: JL
authors.lastname: Solan
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lampe
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001483:Base Sequence; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D055785:Gene Knockdown Techniques; D051528:Guanylate Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008297:Male; D051379:Mice; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D014162:Transfection; D014945:Wound Healing / Q000502:physiology*
chemical_list: C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D018031:Connexin 43; C500216:GJA1 protein, human; C543076:GJA1 protein, mouse; D007136:Immunoglobulins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C106868:CASK kinases; D051528:Guanylate Kinases