Cellular prion protein interaction with vitronectin supports axonal growth and is compensated by integrins.
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.
Hajj
Glaucia N M
GN
Ludwig Institute for Cancer Research, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.
Lopes
Marilene H
MH
Mercadante
Adriana F
AF
Veiga
Silvio S
SS
da Silveira
Rafael B
RB
Santos
Tiago G
TG
Ribeiro
Karina C B
KC
Juliano
Maria A
MA
Jacchieri
Saul G
SG
Zanata
Silvio M
SM
Martins
Vilma R
VR
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*
D016023:Integrins; D018621:PrPC Proteins; D019096:Vitronectin