NR AUJT
AU Vana,K.; Weiss,S.
TI A trans-dominant negative 37kDa/67kDa laminin receptor mutant impairs PrPsc propagation in scrapie-infected neuronal cells
QU Journal of Molecular Biology 2006 Apr 21; 358(1): 57-66
PT journal article
AB The 37kDa/67kDa laminin receptor (LRP/LR) has been identified as a cell surface receptor for cellular and infectious prion proteins. Here, we show that an N-terminally truncated LRP mutant encompassing the extracellular domain of the LRP/LR (LRP102-295::FLAG) reduces the binding of recombinant cellular huPrP to mouse neuroblastoma cells, and infectious moPrP27-30 to BHK cells, and interferes with the PrPsc propagation in scrapie-infected neuroblastoma cells (N2aSc(+)). A cell-free binding assay demonstrated the direct binding of the LRP102-295::FLAG mutant to both PrPc and PrPsc. These results, together with the finding that endogenous LRP levels remain unaffected by the expression of the mutant, indicate that the secreted LRP102-295::FLAG mutant may act in a trans-dominant negative manner as a decoy by trapping PrP molecules. The LRP mutant might represent a potential therapeutic tool for the treatment of TSEs.
MH Animals; Cell-Free System; Cricetinae; Genes, Dominant/*genetics; Humans; Mice; Mice, Mutant Strains; Models, Biological; Mutation/*genetics; Neurons/*metabolism/pathology; PrPc Proteins/metabolism; PrPsc Proteins/*metabolism; Protein Binding; Receptors, Laminin/chemistry/*genetics/*metabolism; Recombinant Fusion Proteins/secretion; Research Support, Non-U.S. Gov't; Scrapie/*metabolism/pathology; Tumor Cells, Cultured
AD Karen Vana und Stefan Weiss (weiss@lmb.uni-muenchen.de), Laboratorium für Molekulare Biologie-Genzentrum-Institut für Biochemie der LMU München, Feodor-Lynen Strasse 25, D-81377 Munich, Germany.
SP englisch
PO England