A trans-dominant negative 37kDa/67kDa laminin receptor mutant impairs PrP(Sc) propagation in scrapie-infected neuronal cells

Journal of Molecular Biology
Karen Vana, Stefan Weiss

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.

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Citations

Jan 19, 2008·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Ane Marcos-CarcavillaMagdalena Serrano
Dec 8, 2006·Cellular and Molecular Neurobiology·Karen VanaStefan Weiss
May 30, 2013·Journal of Molecular Neuroscience : MN·Huinuan WangDeming Zhao
Jun 6, 2012·PloS One·Yoshinori FujimuraHirofumi Tachibana
Sep 21, 2013·International Journal of Molecular Sciences·Liang HuangHoward J Federoff
Aug 7, 2007·Expert Review of Anti-infective Therapy·Heike LudewigsStefan Weiss
Nov 7, 2015·PloS One·Kerrilyn NaidooBoitelo T Letsolo
May 15, 2007·Veterinary Microbiology·Chantal ZuberStefan Weiss
Sep 21, 2013·Scientific Reports·Katarina JovanovicStefan F T Weiss
Oct 20, 2006·Nature·Byron Caughey, Gerald S Baron
Nov 22, 2017·Oncotarget·Tyrone C OtgaarStefan F T Weiss
Nov 30, 2010·Expert Opinion on Therapeutic Patents·Aadilah OmarStefan F T Weiss
May 14, 2019·Journal of Alzheimer's Disease : JAD·Monique J BignouxStefan F T Weiss
Nov 21, 2020·Microbial Pathogenesis·Mengmeng LiuLiancheng Lei
Dec 15, 2010·Journal of the American Chemical Society·Tuane C R G VieiraJerson L Silva

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