Prion protein fragment interacts with PrP-deficient cells.

A fragment of the prion protein (PrP106-126) induces cell death in cultures of wild-type embryonic day (E)16 mouse cortical neurons but not cells derived from mice devoid of cellular PrP(PrPo/o). Two common binding partners for PrP106-126 expressed in both wild-type and PrPo/o mouse brain were isolated and their sequences determined. The two proteins were found to be alpha and beta tubulin. Further evidence that tubulin binds PrP106-126 within cells comes from cell culture experiments. Colchicine toxicity on PrPo/o mouse cortical cells is enhanced by PrP106-126 and taxol enhances toxicity of PrP106-126 on wild-type mouse cortical cells. Our evidence shows that a fragment of PrP can bind a cellular protein and in so doing, alters the metabolism of cells even when they do not express native PrP. This indicates that PrP106-126 is nontoxic to PrPo/o 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.