NR AOTO
AU Hajj,G.N.M.; Lopes,M.H.; Castro,R.M.R.P.S.; Jacchieri,S.; Mercadante,A.F.; Veiga,S.S.; Zanata,S.M.; Martins,V.R.
TI Cellular Prion Protein is a New Receptor for Vitronectin Which Promotes Axonal Growth in Dorsal Root Ganglia
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-01
PT
Konferenz-Poster
AB The cellular prion protein (PrPc) has been described to be involved in several cellular functions, such as protection against oxidative stress and programmed cell death. Its role as a cell surface receptor for laminin and the complex importance on neuronal adhesion, maintenance and differentiation, pointed out for a pleiotrophic function. Herein, we demonstrated that PrPc interacts with another extracellular matrix protein, vitronectin (Vn), with a Kd of 12 nM albeit no association with fibronectin or type IV collagen was observed. We mapped the binding sites at amino acids 105-119 of the PrPc molecule and 307-320 of the Vn molecule. Vn is known to influence many aspects of the nervous system development, in particular, motor neurons differentiation and dorsal root ganglia (DRG) axonal growth. We performed immunohistochemistry for both proteins in mice embryos at day 12.5, since previous reports show the earliest stage of Vn and PrPc expression as embryonic day 10 and 12.5 respectively. The PrPc and Vn distribution pattern is the same; DRG axons and forming axonal fibers are heavily labeled as well as growing nerves however a poorly labeling was observed in neuronal bodies. Therefore, we decided to evaluate the importance of PrPc-Vn interaction in DRG neurons. In these cells, Vn is able to promote neurite extension ranging about 0.8mm long, a phenomenon that can be abrogated by anti-PrPc antibodies. Vn peptide which is the PrPc binding site reproduces the effects observed for the whole Vn molecule. However, these results were not observed in neurons from PrPc null mice ganglia, indicating that this Vn domain specifically binds to PrPc and mediates DRG axonal growth. These data strongly suggest that PrPc can induce specific pathways on neuronal differentiation through distinct protein interactions. Supported by FAPESP
AD Glaucia N.M. Hajj, Vilma R. Martins, Ludwig Institute for Cancer Research, Brazil; Glaucia N.M. Hajj, Adriana F. Mercadante, Universidade de São Paulo, Brazil; Marilene H. Lopes, Rosa M.R.P.S. Castro, Saul Jacchieri, Centro de Tratamento e Pesquisa do Hospital do Cancer, Brazil; Silvio S. Veiga, Silvio M. Zanata, Universidade Federal do Paraná, Brazil
SP englisch
PO Deutschland