Cellular prion protein interaction with vitronectin supports axonal growth and is compensated by integrins

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Hajj, Glaucia N. M. ; Lopes, Marilene H. ; Mercadante, Adriana F. ; Veiga, Silvio S. ; Silveira, Rafael B. da ; Santos, Tiago G. ; Ribeiro, Karina C. B. ; Juliano, Maria A. ; Jacchieri, Saul G. ; Zanata, Silvio M. ; Martins, Vilma R. ^[11]

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cell Science; v. 120, n. 11, p. 1915-1926, May 2007.
• Área do conhecimento: Ciências Biológicas - Bioquímica
• Assunto(s): Gânglios espinhais Matriz extracelular Proteínas Príons Vitronectina Integrinas Neurônios Axônios

Resumo

The physiological functions of the cellular prion protein, PrPC, as a cell surface pleiotropic receptor are under debate. We report that PrPC interacts with vitronectin but not with fibronectin or collagen. The binding sites mediating this PrPC-vitronectin interaction were mapped to residues 105-119 of PrPC 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-PrPC antibodies. Full-length vitronectin, but not the vitronectin peptide 307-320, induced axonal growth of dorsal root neurons from two strains of PrPC-null mice. Functional assays demonstrated that relative to wild-type cells, PrPCnull dorsal root neurons were more responsive to the Arg- Gly-Asp peptide (an integrin-binding site), and exhibited greater ALPHA-v-BETA-3 activity. Our findings indicate that PrPC plays an important role in axonal growth, and this function may be rescued in PrPC-knockout animals by integrin compensatory mechanisms. (AU)

• Processo FAPESP: 99/07124-8 - Papel da proteína prion celular em processos fisiológicos e patológicos
• Beneficiário: Vilma Regina Martins
• Linha de fomento: Auxílio à Pesquisa - Temático