Function of Cellular Prion Protein
Takashi Onodera, Katsuaki Sugiura, Shigeru Matsuda and Akikazu Sakudo
from: Prions: Current Progress in Advanced Research (Edited by: Akikazu Sakudo and Takashi Onodera). Caister Academic Press, U.K. (2013)
Although much is known about the effect of PrPSc in prion diseases, the normal function of PrPC is poorly understood. PrPC may act as an antiapoptotic agent by blocking some of the internal environmental factors that initiate apoptosis. PrP-knockout methods provide powerful hints on the neuroprotective function of PrPC. Using PrPC-knockout cell lines, the inhibition of apoptosis through STI1 is mediated by PrPC-dependent SOD activation. Recently several reports show that PrPC participate in trans-membrane signaling process associated with hematopoietic stem cell replication and neuronal differentiation. Besides PrP-knockout exhibited wide spread alterations of oscillatory activity in the olfactory bulb as well as altered paired-pulse plasticity at the dendrodendric synapse. Both the behavioral and electro-physiological phenotypes could be rescued by neuronal PrPC expression. Neuprotein Shadoo (Sho), similarly to PrPC, can prevent neuronal cell death induced by the expression of PrP△HD mutants, an artificial PrP mutant devoid of internal hydrophobic domain. Sho can efficiently protect cells against exito-toxin-induced cell death by glutamates. Sho and PrP seem to be dependent on similar domains, in particular N-terminal (N) and their internal hydrophobic domain. Sho△N and Sho△HD displayed a reduced stress-protective activity but are complex glycosylated and attached to outer leaflet of the plasma membrane via GPI anchor indicating that impaired activity is not due to incorrect cellular trafficking. In Shadoo over-expressed mice showed large amyloid plaques not seen in wild-type mice. However Shadoo is not a major modulator of PrPSc accumulation and scrapie pathogenesis. Sho and PrP share a stress-protective activity. The ability to adopt a toxic conformation of PrPSc seems to be specific for PrP read more ...