NR AOVZ
AU Lopes,M.H.; Hajj,G.N.M.; Castro,R.M.R.P.S.; Muras,A.G.; Brentani,R.R.; Martins,V.R.
TI Importance of the PrPc-STI1 Interaction for Neuronal Plasticity Mechanisms
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-81
PT Konferenz-Poster
AB Our group has been investigating the involvement of cellular prion protein (PrPc) and its ligands in neuronal plasticity. Recently, we have verified that PrPc binds STI1 (stress inducible protein 1) and that this complex transduces signals through MAPK and PKA, the later being responsible for the rescue of neurons from apoptosis (EMBO J. 21(13):3307-16; 3317-3326, 2002). Immunohistochemistry assays demonstrated that PrPc and STI1 are expressed in mice embryonic neurons from Central (CNS) and Peripheral Nervous System (PNS). Herein, our objectives were to evaluate the role of this interaction in neurite growth, both in the CNS and PNS. Thus, we treated primary cultures of hippocampal and dorsal root ganglia (DRG) neurons from wild-type and PrPc ablated (Prn-p0/0) mice embryos with STI1. After 6 hours, the treatment was able to elicit neuritogenesis in a dose dependent manner in wild-type hippocampal and DRG neurons, but not in Prn-p0/0 cells, indicating that the event is dependent on PrPc expression. Furthermore, we have also demonstrated that PrPc was able to promote neuritogenesis through its interaction with laminin (LN) (Mol. Brain. Res.76:85-92, 2000). Interestingly, the STI1 and LN binding sites are mapped between amino acids 113-128 and 162-192 of the PrPc, respectively. Therefore, we decided to investigate if these two proteins can cooperate on PrPc dependent neuronal plasticity. DRG neurons were plated over a low concentration of LN in the presence of increasing STI1 concentrations and after 2 hours of treatment we observed a surprisingly high effect on neurite outgrowth only on wild-type cells. When each one of the proteins is separately added an almost null effect is observed. Therefore, our data indicates that STI1 binding to PrPc induces neurite formation in hippocampal and sensory neurons, and that this event is synergized by LN in sensory neurons. Supported by FAPESP.
AD Marilene Hohmuth Lopes, Rosa Maria Rodrigues Pinto Santos Castro, Angelita Gonzales Muras, Ricardo Renzo Brentani, Vilma Regina Martins, Ludwig Institute for Cancer Research, Sao Paulo, Brazil and Centro de Tratamento e Pesquisa- Hospital do Câncer- Sao Paulo, Brazil; Glaucia Noeli Maroso Hajj, Ludwig Institute for Cancer Research, Sao Paulo, Brazil and Universidade de São Paulo, Brazil
SP englisch
PO Deutschland