Prion protein fragment interacts with PrP-deficient cells

✍ Scribed by David R. Brown; Bernhard Schmidt; Hans A. Kretzschmar

• Book ID: 101245566
• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 138 KB
• Volume: 52
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19980501)52:3<260::aid-jnr2>3.0.co;2-b

✦ Synopsis

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(PrP o/o) . Two common binding partners for PrP106-126 expressed in both wild-type and PrP o/o mouse brain were isolated and their sequences determined. The two proteins were found to be ␣ and ␤ tubulin. Further evidence that tubulin binds PrP106-126 within cells comes from cell culture experiments. Colchicine toxicity on PrP o/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 PrP o/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.