Similar turnover and shedding of the cellular prion protein in primary lymphoid and neuronal cells

The cellular prion protein (PrPc) is essential for pathogenesis and transmission of prion diseases. Although prion replication in the brain is accompanied by neurodegeneration, prions multiply efficiently in the lymphoreticular system without any detectable pathology. We have used pulse-chase metabolic radiolabeling experiments to investigate the turnover and processing of PrPc in primary cell cultures derived from lymphoid and nervous tissues. Similar kinetics of PrPc degradation were observed in these tissues. This indicates that the differences between these two organs with respect to their capacity to replicate prions is not due to differences in the turnover of PrPc. Substantial amounts of a soluble form of PrP that lacks the glycolipid anchor appeared in the medium of splenocytes and cerebellar granule cells. Soluble PrP was detected in murine and human serum, suggesting that it might be of physiological relevance.