Doppel and PrPC do not share the same membrane microenvironment

Doppel is a paralog of the normal prion protein, PrPC. It has been suggested that Doppel can compensate for the absence of PrPC in PrP0/0 mice. In this work, we tested whether Doppel and PrPC share the same cell location, thereby sharing the same neighboring cell components, probably required to share the same cell function. Our results show that, at detergent conditions in which membrane rafts were intact, neither PrPC and Doppel co-immunoprecipitate with the appropriate antibodies, nor was Doppel retained by a Cu2+ IMAC resin, as PrPC does. This indicates that, although Doppel is a raft-associated protein as is PrPC, both proteins are not present in the same membrane microenvironment, and they probably do not perform the same function. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.