the toxicity of a mutant prion protein is cell-autonomous, and can be suppressed by wild-type prion protein on adjacent cells的毒性变异朊蛋白是细胞自动,并且可以抑制野生型朊蛋白在相邻细胞.pdfVIP

The Toxicity of a Mutant Prion Protein Is Cell- Autonomous, and Can Be Suppressed by Wild-Type Prion Protein on Adjacent Cells 1,2,3 . 1. 1,2,4 3 3 Emiliano Biasini * , Jessie A. Turnbaugh , Tania Massignan , Pietro Veglianese , Gianluigi Forloni , 2,4 2,3 1 Valentina Bonetto , Roberto Chiesa , David A. Harris * 1 Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts, United States of America, 2 Dulbecco Telethon Institute, Milan, Italy, 3 Department of Neuroscience, Mario Negri Institute, Milan, Italy, 4 Department of Biochemistry and Molecular Pharmacology, Mario Negri Institute, Milan, Italy Abstract C Insight into the normal function of PrP , and how it can be subverted to produce neurotoxic effects, is provided by PrP molecules carrying deletions encompassing the conserved central region. The most neurotoxic of these mutants, D105–125 (called DCR), produces a spontaneous neurodegenerative illness when expressed in transgenic mice, and this phenotype can be dose-dependently suppressed by co-expression of wild-type PrP. Whether the toxic activity of DCR PrP and the protective activity or wild-type PrP are cell-autonomous, or can be exerted on neighboring cells, is unknown. To investigate this question, we have utilized co-cultures of differentiated neural stem cells derived from mice expressing DCR or wild-type PrP. Cells from the two kinds of mice, which are marked by the presence or absence of GFP, are differentiated together to yield neurons, astrocytes, and oligodendrocytes. As a su