NR AWEW
AU Fioriti,L.; Airaghi,S.; Forloni,G.; Chiesa,R.
TI Cell type-specific neuroprotective activity of untranslocated prion protein in primary neurons
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions CE-14
PT Konferenz-Poster
AB A cytosolic form of the prion protein (PrP) has been proposed to play a key pathogenic role in prion diseases. However, the consequence of PrP localization in the cytosol of neurons remains unclear, having either cytotoxic or anti-apoptotic effects been reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also controversial, since both retrograde transport from the endoplasmic reticulum and abortive translocation have been proposed. In view of the physio-pathological interest of cytosolic PrP, we systematically investigated its biogenesis and effect on survival of cortical, hippocampal and cerebellar granule neurons cultured from newborn mice. We find that the proteasome inhibitors cause accumulation of an unglycosylated form of PrP in cortical and hippocampal, but not in cerebellar neurons. We provide evidence that this form contains uncleaved signal peptides, indicating that it corresponds to PrP molecules that have not co-transationally translocated into the endoplasmic reticulum lumen. Analysis of cell viability shows that neurons accumulating untranslocated PrP are more resistant to proteasome inhibitors' toxicity than neurons that do not synthesize this topological variant. These findings indicate differences in the efficiency of co-translational translocation of PrP between distinct neuronal types, and underscore a potential physiological role of cytosolic PrP.
AD L. Fioriti, S. Airaghi: Dulbecco Telethon Institute and Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; G. Forloni: Dulbecco Telethon Institute, Milan, Italy; R. Chiesa: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. E-mail: chiesa@marionegri.it
SP englisch
PO Italien