title: aPKC phosphorylates JAM-A at Ser285 to promote cell contact maturation and tight junction formation.
abstract: The PAR-3-atypical protein kinase C (aPKC)-PAR-6 complex has been implicated in the development of apicobasal polarity and the formation of tight junctions (TJs) in vertebrate epithelial cells. It is recruited by junctional adhesion molecule A (JAM-A) to primordial junctions where aPKC is activated by Rho family small guanosine triphosphatases. In this paper, we show that aPKC can interact directly with JAM-A in a PAR-3-independent manner. Upon recruitment to primordial junctions, aPKC phosphorylates JAM-A at S285 to promote the maturation of immature cell-cell contacts. In fully polarized cells, S285-phosphorylated JAM-A is localized exclusively at the TJs, and S285 phosphorylation of JAM-A is required for the development of a functional epithelial barrier. Protein phosphatase 2A dephosphorylates JAM-A at S285, suggesting that it antagonizes the activity of aPKC. Expression of nonphosphorylatable JAM-A/S285A interferes with single lumen specification during cyst development in three-dimensional culture. Our data suggest that aPKC phosphorylates JAM-A at S285 to regulate cell-cell contact maturation, TJ formation, and single lumen specification.
authors.affiliation: Institute-associated Research Group: Cell adhesion and cell polarity, University Münster, 48419 Münster, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Iden
authors.forename: Steve
authors.initials: S
authors.lastname: Misselwitz
authors.forename: Swetha S D
authors.initials: SS
authors.lastname: Peddibhotla
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Tuncay
authors.forename: Daniela
authors.initials: D
authors.lastname: Rehder
authors.forename: Volker
authors.initials: V
authors.lastname: Gerke
authors.forename: Horst
authors.initials: H
authors.lastname: Robenek
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Klaus
authors.initials: K
authors.lastname: Ebnet
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000378:metabolism; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D019108:Tight Junctions / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; C498686:F11r protein, mouse; D011956:Receptors, Cell Surface; D012694:Serine; C115015:PKC-3 protein; D011493:Protein Kinase C; D054648:Protein Phosphatase 2