NR AOST
AU Freitas,A.R.O.; Hässig,R.; Laffont,I.; Martins,V.R.; Moya,K.L.
TI The PrPc interacting protein, STI1, in peripheral nerve
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-68
PT Konferenz-Poster
AB
The prion protein PrPsc has been the center of intense research due to its implication in transmissible spongiform encephalopathies (TSE). Post-translational modifications of the endogenous cellular form, PrPc, by unclear mechanisms lead PrPsc accumulation in the brain during TSE. PrPc is a glycoprotein abundant in plastic regions of the brain where it can be observed in synapses. Like other proteins found in the nerve terminal, PrPc is synthesized in the cell body and rapidly anterogradely transported down the axons. Recently, a new molecular partner of PrPc, Stress Inducible Protein 1 (STI1), was identified. This 60 KDa protein interacts with PrPc in a specific and high-affinity manner. This interaction induces neuroprotective signals that rescue cells from apoptosis. Despite the absence of a transmembrane domain or a signal peptide, the STI1 protein is found at the cell surface. Thus, we hypothesized that STI1 is transported to the cell membrane with other membrane proteins, namely, PrPc.
In order to begin to investigate this, we used the sciatic nerve test section/accumulation model in hamsters and in rats. In this model a 2 mm basal segment containing stationary and slowly transported axonal proteins was removed. 24 h later, a 2 mm segment proximal to the cut was removed. In this model the proximal segment contains anterogradely transported proteins that accumulate during the 24h period in addition to stationary proteins. One-D Western blot analysis showed an increase in the signal intensity in the proximal segment compared to the basal segment. This is consistent with a 24h accumulation of STI1 and suggests that STI1 is anterogradely transported in axons. Further studies are needed to determine if STI1 is transported in association with PrPc and to characterize the axonal membrane compartment containing STI1.
Support: FAPESP, Institute Ludwig and GIS "Infections à prions".
AD Adriana R.O. Freitas, Raymonde Hässig, Isabelle Laffont, Kenneth L. Moya, CEA-CNRS URA 2210, Service Hospitalier Frederic Joliot, France; Adriana R.O. Freitas, Vilma R. Martins, Ludwig Institute for Cancer Research - Sao Paulo Branch, Brazil
SP englisch
PO Deutschland