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.
Brown
D R
DR
Department of Biochemistry and MRC Cambridge Centre for Brain Repair, Cambridge University, Cambridge, United Kingdom. drb@cam.ac.uk
D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D003300:Copper / Q000493:pharmacokinetics*; D003301:Copper Radioisotopes; D003600:Cytosol / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D018621:PrPC Proteins / Q000235:genetics* / Q000378:metabolism*; D011233:Precipitin Tests; D013997:Time Factors; D014701:Veratridine / Q000494:pharmacology*
D003301:Copper Radioisotopes; D018621:PrPC Proteins; D014701:Veratridine; D003300:Copper