Prion protein expression aids cellular uptake and veratridine-induced release of copper

The function of the prion protein is unknown despite suggestions it binds copper. Radioactive copper (Cu(67)) was used to demonstrate that histidine-dependent uptake of copper by cerebellar cells in culture is related to the level of PrP(c) expression. Copper is released by neurones at the synapse. Veratridine-induced release from synapses was proportional to the level of PrP(c) expression. Veratridine-induced release can be abolished only from PrP(c) expressing cells by pretreatment with phosphatidyl-specific phospholipase C, an enzyme that cleaves PrP(c) from the cell surface. These results suggest that PrP(c) aids cellular copper uptake and may have a function at the synapse related to release of copper during transmission.