Cellular prion protein interaction with vitronectin supports axonal growth and is compensated by integrins.
J Cell Sci
; 120(Pt 11): 1915-26, 2007 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-17504807
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Axônios
/
Integrinas
/
Proteínas PrPC
/
Vitronectina
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Reino Unido