PRION PROTEIN-FRAGMENT INTERACTS WITH PRP-DEFICIENT CELLS

A fragment of the prion protein (PrP106-126) induces cell death in cul tures of wild-type embryonic day (E)16 mouse cortical neurons but not cells derived from mice devoid of cellular PrP(PrP0/0). Two common bin ding partners for PrP106-126 expressed in both wild-type and PrP0/0 mo use brain were isolated and their sequences determined. The two protei ns were found to be alpha and beta tubulin. Further evidence that tubu lin binds PrP106-126 within cells comes from cell culture experiments. Colchicine toxicity on PrP0/0 mouse cortical cells is enhanced by PrP 106-126 and taxol enhances toxicity of PrP106-126 on wild-type mouse c ortical cells. Our evidence shows that a fragment of PrP can bind a ce llular protein and in so doing, alters the metabolism of cells even wh en they do not express native PrP, This indicates that PrP106-126 is n ontoxic to PrP0/0 cells, not because of an inability to interact with these cells but because of the loss of some aspect of a PrP expression -dependent phenotype. (C) 1998 Wiley-Liss, Inc.