title: Cellular prion protein interaction with vitronectin supports axonal growth and is compensated by integrins.
abstract: The physiological functions of the cellular prion protein, PrP(C), as a cell surface pleiotropic receptor are under debate. We report that PrP(C) interacts with vitronectin but not with fibronectin or collagen. The binding sites mediating this PrP(C)-vitronectin interaction were mapped to residues 105-119 of PrP(C) and the residues 307-320 of vitronectin. The two proteins were co-localized in embryonic dorsal root ganglia from wild-type mice. Vitronectin addition to cultured dorsal root ganglia induced axonal growth, which could be mimicked by vitronectin peptide 307-320 and abrogated by anti-PrP(C) antibodies. Full-length vitronectin, but not the vitronectin peptide 307-320, induced axonal growth of dorsal root neurons from two strains of PrP(C)-null mice. Functional assays demonstrated that relative to wild-type cells, PrP(C)-null dorsal root neurons were more responsive to the Arg-Gly-Asp peptide (an integrin-binding site), and exhibited greater alphavbeta3 activity. Our findings indicate that PrP(C) plays an important role in axonal growth, and this function may be rescued in PrP(C)-knockout animals by integrin compensatory mechanisms.
authors.affiliation: Ludwig Institute for Cancer Research, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.
authors.forename: Glaucia N M
authors.initials: GN
authors.lastname: Hajj
authors.forename: Marilene H
authors.initials: MH
authors.lastname: Lopes
authors.forename: Adriana F
authors.initials: AF
authors.lastname: Mercadante
authors.forename: Silvio S
authors.initials: SS
authors.lastname: Veiga
authors.forename: Rafael B
authors.initials: RB
authors.lastname: da Silveira
authors.forename: Tiago G
authors.initials: TG
authors.lastname: Santos
authors.forename: Karina C B
authors.initials: KC
authors.lastname: Ribeiro
authors.forename: Maria A
authors.initials: MA
authors.lastname: Juliano
authors.forename: Saul G
authors.initials: SG
authors.lastname: Jacchieri
authors.forename: Silvio M
authors.initials: SM
authors.lastname: Zanata
authors.forename: Vilma R
authors.initials: VR
authors.lastname: Martins
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D018621:PrPC Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D019096:Vitronectin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016023:Integrins; D018621:PrPC Proteins; D019096:Vitronectin