title: Prion protein fragment interacts with PrP-deficient cells.
abstract: 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.
authors.affiliation: Institut für Neuropathologie, Universität Göttingen, Germany. drb33@cam.ac.uk
authors.forename: D R
authors.initials: DR
authors.lastname: Brown
authors.forename: B
authors.initials: B
authors.lastname: Schmidt
authors.forename: H A
authors.initials: HA
authors.lastname: Kretzschmar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D002478:Cells, Cultured; D003078:Colchicine / Q000633:toxicity; D004357:Drug Synergism; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011328:Prions / Q000378:metabolism* / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D011328:Prions; D014404:Tubulin; C082632:prion protein (106-126); D017239:Paclitaxel; D003078:Colchicine