title: The BAR domain protein PICK1 regulates cell recognition and morphogenesis by interacting with Neph proteins.
abstract: Neph proteins are evolutionarily conserved membrane proteins of the immunoglobulin superfamily that control the formation of specific intercellular contacts. Cell recognition through these proteins is essential in diverse cellular contexts such as patterning of the compound eye in Drosophila melanogaster, neuronal connectivity in Caenorhabditis elegans, and the formation of the kidney filtration barrier in mammals. Here we identify the PDZ and BAR domain protein PICK1 (protein interacting with C-kinase 1) as a Neph-interacting protein. Binding required dimerization of PICK1, was dependent on PDZ domain protein interactions, and mediated stabilization of Neph1 at the plasma membrane. Moreover, protein kinase C (PKCα) activity facilitated the interaction through releasing Neph proteins from their binding to the multidomain scaffolding protein zonula occludens 1 (ZO-1), another PDZ domain protein. In Drosophila, the Neph homologue Roughest is essential for sorting of interommatidial precursor cells and patterning of the compound eye. RNA interference-mediated knockdown of PICK1 in the Drosophila eye imaginal disc caused a Roughest destabilization at the plasma membrane and a phenotype that resembled rst mutation. These data indicate that Neph proteins and PICK1 synergistically regulate cell recognition and contact formation.
authors.affiliation: Renal Division, Department of Medicine and Center for Molecular Medicine, University of Cologne, 50937 Cologne, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Höhne
authors.forename: Johannes
authors.initials: J
authors.lastname: Lorscheider
authors.forename: Anna
authors.initials: A
authors.lastname: von Bardeleben
authors.forename: Matthias
authors.initials: M
authors.lastname: Dufner
authors.forename: M Antonia
authors.initials: MA
authors.lastname: Scharf
authors.forename: Markus
authors.initials: M
authors.lastname: Gödel
authors.forename: Martin
authors.initials: M
authors.lastname: Helmstädter
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Schurek
authors.forename: Sibylle
authors.initials: S
authors.lastname: Zank
authors.forename: Peter
authors.initials: P
authors.lastname: Gerke
authors.forename: Christine
authors.initials: C
authors.lastname: Kurschat
authors.forename: Sema Hayriye
authors.initials: SH
authors.lastname: Sivritas
authors.forename: Elke
authors.initials: E
authors.lastname: Neumann-Haefelin
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Huber
authors.forename: H Christian
authors.initials: HC
authors.lastname: Reinhardt
authors.forename: Astrid C
authors.initials: AC
authors.lastname: Schauss
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schermer
authors.forename: Karl-Friedrich
authors.initials: KF
authors.lastname: Fischbach
authors.forename: Thomas
authors.initials: T
authors.lastname: Benzing
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002450:Cell Communication; D004330:Drosophila; D004331:Drosophila melanogaster; D005123:Eye / Q000166:cytology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009024:Morphogenesis; D009687:Nuclear Proteins / Q000502:physiology*; D054731:PDZ Domains; D011485:Protein Binding; D011493:Protein Kinase C; D055503:Protein Multimerization; D055550:Protein Stability; D017434:Protein Structure, Tertiary
chemical_list: D002352:Carrier Proteins; C431137:KIRREL1 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; C498297:PICk1 protein, human; D011493:Protein Kinase C