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First published online 15 May 2007
doi: 10.1242/jcs.03459

Journal of Cell Science 120, 1915-1926 (2007)
Published by The Company of Biologists 2007
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Research Article

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

Glaucia N. M. Hajj1,2, Marilene H. Lopes1,3, Adriana F. Mercadante4, Silvio S. Veiga5, Rafael B. da Silveira5, Tiago G. Santos1,3, Karina C. B. Ribeiro3, Maria A. Juliano6, Saul G. Jacchieri3, Silvio M. Zanata4 and Vilma R. Martins1,*

1 Ludwig Institute for Cancer Research, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
2 Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil
3 Centro de Tratamento e Pesquisa Hospital do Câncer, São Paulo, Brazil
4 Departamento de Patologia Básica, Universidade Federal do Paraná, Curitiba, Brazil
5 Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Brazil
6 INFAR, Universidade Federal de São Paulo, São Paulo, Brazil

* Author for correspondence (e-mail: vmartins{at}ludwig.org.br)

Accepted 11 April 2007

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}vbeta3 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.

Key words: Dorsal root ganglia, Extracellular matrix, Cellular prion protein, Vitronectin, Axon growth, Integrins




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[Abstract] [Full Text] [PDF]


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