title: The human PDZome: a gateway to PSD95-Disc large-zonula occludens (PDZ)-mediated functions.
abstract: Protein-protein interactions organize the localization, clustering, signal transduction, and degradation of cellular proteins and are therefore implicated in numerous biological functions. These interactions are mediated by specialized domains able to bind to modified or unmodified peptides present in binding partners. Among the most broadly distributed protein interaction domains, PSD95-disc large-zonula occludens (PDZ) domains are usually able to bind carboxy-terminal sequences of their partners. In an effort to accelerate the discovery of PDZ domain interactions, we have constructed an array displaying 96% of the human PDZ domains that is amenable to rapid two-hybrid screens in yeast. We have demonstrated that this array can efficiently identify interactions using carboxy-terminal sequences of PDZ domain binders such as the E6 oncoviral protein and protein kinases (PDGFRβ, BRSK2, PCTK1, ACVR2B, and HER4); this has been validated via mass spectrometry analysis. Taking advantage of this array, we show that PDZ domains of Scrib and SNX27 bind to the carboxy-terminal region of the planar cell polarity receptor Vangl2. We also have demonstrated the requirement of Scrib for the promigratory function of Vangl2 and described the morphogenetic function of SNX27 in the early Xenopus embryo. The resource presented here is thus adapted for the screen of PDZ interactors and, furthermore, should facilitate the understanding of PDZ-mediated functions.
authors.affiliation: CRCM, Equipe labellisée Ligue Contre le Cancer, Inserm, U1068, CRCM, Marseille, F-13009, France.
authors.forename: Edwige
authors.initials: E
authors.lastname: Belotti
authors.forename: Jolanta
authors.initials: J
authors.lastname: Polanowska
authors.forename: Avais M
authors.initials: AM
authors.lastname: Daulat
authors.forename: Stéphane
authors.initials: S
authors.lastname: Audebert
authors.forename: Virginie
authors.initials: V
authors.lastname: Thomé
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lissitzky
authors.forename: Frédérique
authors.initials: F
authors.lastname: Lembo
authors.forename: Karim
authors.initials: K
authors.lastname: Blibek
authors.forename: Shizue
authors.initials: S
authors.lastname: Omi
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lenfant
authors.forename: Akanksha
authors.initials: A
authors.lastname: Gangar
authors.forename: Mireille
authors.initials: M
authors.lastname: Montcouquiol
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Santoni
authors.forename: Michael
authors.initials: M
authors.lastname: Sebbagh
authors.forename: Michel
authors.initials: M
authors.lastname: Aurrand-Lions
authors.forename: Stéphane
authors.initials: S
authors.lastname: Angers
authors.forename: Laurent
authors.initials: L
authors.lastname: Kodjabachian
authors.forename: Jérome
authors.initials: J
authors.lastname: Reboul
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Borg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002465:Cell Movement; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005453:Fluorescence; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D054731:PDZ Domains; D025941:Protein Interaction Mapping; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D015203:Reproducibility of Results; D058305:Sorting Nexins / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D014981:Xenopus / Q000196:embryology / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D020543:Proteome; C480591:SCRIB protein, human; C522885:SNX27 protein, human; D058305:Sorting Nexins; D025521:Tumor Suppressor Proteins; C468513:VANGL2 protein, human; D011494:Protein Kinases