title: A trans-dominant negative 37kDa/67kDa laminin receptor mutant impairs PrP(Sc) propagation in scrapie-infected neuronal cells.
abstract: 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 PrP(Sc) propagation in scrapie-infected neuroblastoma cells (N2aSc(+)). A cell-free binding assay demonstrated the direct binding of the LRP102-295::FLAG mutant to both PrP(c) and PrP(Sc). 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.
authors.affiliation: Laboratorium für Molekulare Biologie-Genzentrum-Institut für Biochemie der LMU München, Feodor-Lynen Strasse 25, D-81377 Munich, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Vana
authors.forename: Stefan
authors.initials: S
authors.lastname: Weiss
mesh_terms: D000818:Animals; D002474:Cell-Free System; D006224:Cricetinae; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018621:PrPC Proteins / Q000378:metabolism; D018620:PrPSc Proteins / Q000378:metabolism*; D011485:Protein Binding; D017474:Receptors, Laminin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins; D017474:Receptors, Laminin; D011993:Recombinant Fusion Proteins