NR AXFJ
AU Hajj,G.N.M.; Lopes,M.H.; Mercadante,A.F.; Veiga,S.S.; da Silveira,R.B.; Santos,T.G.; Ribeiro,K.C.B.; Juliano,M.A.; Jacchieri,S.G.; Zanata,S.M.; Martins,V.R.
TI Cellular prion protein interaction with vitronectin supports axonal growth and is compensated by integrins
QU Journal of Cell Science 2007 Jun 1; 120(11): 1915-26
PT journal article; research support, non-u.s. gov't
AB 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 alphavbeta3 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.
MH Animals; Axons/*metabolism; Binding Sites; Cell Line; Embryo/cytology/metabolism; Ganglia, Spinal/cytology/embryology; Humans; Integrins/*metabolism; Mice; PrPc Proteins/chemistry/*metabolism; Protein Binding; Protein Interaction Mapping; Protein Structure, Tertiary; Vitronectin/chemistry/*metabolism
AD Ludwig Institute for Cancer Research, Hospital Alemao Oswaldo Cruz, Sao Paulo, Brazil.
SP englisch
PO England
EA pdf-Datei, Supplement Abb. 1, Supplement Abb. 2, Supplement Abb. 3, Supplement Abb. 4 und Legenden