title: The 37/67 kDa laminin receptor (LR) inhibitor, NSC47924, affects 37/67 kDa LR cell surface localization and interaction with the cellular prion protein.
abstract: The 37/67 kDa laminin receptor (LR) is a non-integrin protein, which binds both laminin-1 of the extracellular matrix and prion proteins, that hold a central role in prion diseases. The 37/67 kDa LR has been identified as interactor for the prion protein (PrP(C)) and to be required for pathological PrP (PrP(Sc)) propagation in scrapie-infected neuronal cells, leading to the possibility that 37/67 kDa LR-PrP(C) interaction is related to the pathogenesis of prion diseases. A relationship between 37/67 kDa LR and PrP(C) in the presence of specific LR inhibitor compounds has not been investigated yet. We have characterized the trafficking of 37/67 kDa LR in both neuronal and non-neuronal cells, finding the receptor on the cell surface and nuclei, and identified the 67 kDa LR as the almost exclusive isoform interacting with PrP(C). Here, we show that the treatment with the 37/67 kDa LR inhibitor, NSC47924, affects both the direct 37/67 kDa LR-PrP(C) interaction in vitro and the formation of the immunocomplex in live cells, inducing a progressive internalization of 37/67 kDa LR and stabilization of PrP(C) on the cell surface. These data reveal NSC47924 as a useful tool to regulate PrP(C) and 37/67 kDa LR trafficking and degradation, representing a novel small molecule to be tested against prion diseases.
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131, Naples, Italy.|Ceinge-Biotecnologie Avanzate scarl, 80145, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sarnataro
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pepe
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II", 80137, Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Altamura
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131, Naples, Italy.
authors.forename: Imma
authors.initials: I
authors.lastname: De Simone
authors.affiliation: Department of Translational Medical Sciences, University of Naples "Federico II", 80131, Naples, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Pesapane
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131, Naples, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Nitsch
authors.affiliation: Department of Translational Medical Sciences, University of Naples "Federico II", 80131, Naples, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Montuori
authors.affiliation: Department of Pharmacy, "Drug Discovery" Laboratory, University of Naples "Federico II", 80131, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavecchia
authors.affiliation: Institut Pasteur, Unité de Trafic Membranaire et Pathogénèse, 75724 Paris CEDEX 15, France.
authors.forename: Chiara
authors.initials: C
authors.lastname: Zurzolo
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary; D024202:Electrophoretic Mobility Shift Assay; D057809:HEK293 Cells; D006801:Humans; D009284:Naphthols / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D000072002:Prion Proteins / Q000378:metabolism*; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism*
chemical_list: C000616612:1-((4-methoxyanilino)methyl)-2-naphthol; D000814:Aniline Compounds; D018076:DNA, Complementary; D009284:Naphthols; D000072002:Prion Proteins; D017474:Receptors, Laminin