NR ATGV
AU Beranger,F.; Vezilier,J.; Delfieu,V.; Onodera,T.; Lehmann,S.L.
TI The 23-230 truncated prion protein is localized to the nucleus independently of its nuclear localization signals and affects cytokinesis
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-01
PT Konferenz-Poster
AB The cellular mechanisms of prion-induced neurological dysfunction are poorly understood. Transgenic mice expressing a truncated form of the prion protein (23-230 PrP, devoid of the N-terminal peptide signal and GPI anchor), develop normally but acquire cerebellar degeneration and gliosis, characteristic of prion diseases (Ma,J. and Lindquist,S., Science, 2002). In order to decipher the putative mechanisms of neurodegeneration induced by 23-230 PrP, we established, with lentiviral expression vectors, inducible cell lines expressing this truncated form of PrP. We derived these inducible cell lines from either Npl1 hippocampal prnp-/- cells or from neuroblastoma N2a cells. We found that 23-230 PrP, which was expected to be cytosolic, accumulates instead in the nucleus of the cells. We report that nuclear localization of this mutant form of PrP is independent of its nuclear localization signals (NLS). We determined that 23-230 PrP interacts with chromatin in vivo, as already described for recombinant PrP and for PrPsc, and interestingly, induces the formation of multinucleated cells.
AD F.Béranger, J.Vézilier, V.Delfieu, S.Lehmann, Institut de Génétique Humaine, CNRS UPR 1142, 141 Rue de la Cardonille, 34396 Montpellier, France; T.Onodera, Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo 113-8657, Japan
SP englisch
PO Deutschland