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

• Autor(a) principal: Hajj, Glaucia N. M.
• Data de Publicação: 2007
• Outros Autores: Lopes, Marilene H., Mercadante, Adriana F., Veiga, Silvio Sanches [UNIFESP], Silveira, Rafael Bertoni da [UNIFESP], Santos, Tiago G., Ribeiro, Karina C. B., Juliano, Maria Aparecida [UNIFESP], Jacchieri, Saul G., Zanata, Silvio M., Martins, Vilma R.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• dARK ID: ark:/48912/0013000006t75
• Texto Completo: http://dx.doi.org/10.1242/jcs.03459; http://repositorio.unifesp.br/handle/11600/29775
• topic: dorsal root ganglia; extracellular matrix; cellular prion protein; vitronectin; axon growth; integrins

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, PrPC-null 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.