1. The 37/67kDa laminin receptor (LR) inhibitor, NSC47924, affects 37/67kDa LR cell surface localization and interaction with the cellular prion protein
- Author
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Lucio Nitsch, Anna Pepe, Antonio Lavecchia, Ada Pesapane, Imma De Simone, Gennaro Altamura, Nunzia Montuori, Daniela Sarnataro, Chiara Zurzolo, University of Naples Federico II = Università degli studi di Napoli Federico II, CEINGE - Biotecnologie Avanzate, Trafic membranaire et Pathogénèse, Institut Pasteur [Paris] (IP), This work has been supported in part by POR Campania FSE 2007–2013, Project CREME, by Ministero per l’Università e la Ricerca Scientifica, PRIN 2010–2011 and Campania Bioscience Grant PON03PE_0060_08 and research grants to C.Z. from European Commission FP7 PRIORITY 222887, MI CARNOT ICSA/PMI, grants from the region Ile-de-France (IDF DIM-MALINF 2013) and Equipe FRM (Fondation Recherche Medicale) 2014 (DEQ20140329557)., European Project: 222887,EC:FP7:KBBE,FP7-KBBE-2007-2A,PRIORITY(2009), Sarnataro, Daniela, Pepe, Anna, Altamura, Gennaro, De Simone, Imma, Pesapane, Ada, Nitsch, Lucio, Montuori, Nunzia, Lavecchia, Antonio, and Zurzolo, Chiara
- Subjects
0301 basic medicine ,MESH: Decision Making ,MESH: Community Participation ,LRP/LR ,animal diseases ,INVASION ,Cell ,PRPSC PROPAGATION ,Electrophoretic Mobility Shift Assay ,Naphthols ,Pathogenesis ,Extracellular matrix ,MESH: Physicians ,Internalization ,Receptor ,Lipid raft ,media_common ,Neurons ,Aniline Compounds ,Multidisciplinary ,ALZHEIMERS-DISEASE ,medicine.anatomical_structure ,MESH: Faculty, Medical ,MESH: American Medical Association ,MESH: Germany, West ,ANTIBODY IGG1-IS18 ,Gene isoform ,MESH: Social Dominance ,DNA, Complementary ,media_common.quotation_subject ,MESH: Education, Medical ,MESH: Societies, Medical ,MESH: Government ,MESH: Social Control, Formal ,Biology ,MESH: Insurance, Health ,Prion Proteins ,Article ,Receptors, Laminin ,03 medical and health sciences ,MESH: Personal Satisfaction ,medicine ,MESH: United States ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,PRECURSOR ,SCRAPIE-INFECTED MICE ,MESH: Humans ,MESH: Schools, Medical ,Cell Membrane ,INDUCED CYTOTOXICITY ,MESH: Legislation, Medical ,MESH: Medicine ,Molecular biology ,In vitro ,nervous system diseases ,MESH: Licensure, Medical ,LIPID RAFTS ,HEK293 Cells ,030104 developmental biology ,MESH: Politics ,MESH: Economics, Medical ,INTERNALIZATION ,MESH: Private Practice ,MESH: Institutional Practice - 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 (PrPC) and to be required for pathological PrP (PrPSc) propagation in scrapie-infected neuronal cells, leading to the possibility that 37/67 kDa LR-PrPC interaction is related to the pathogenesis of prion diseases. A relationship between 37/67 kDa LR and PrPC 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 PrPC. Here, we show that the treatment with the 37/67 kDa LR inhibitor, NSC47924, affects both the direct 37/67 kDa LR-PrPC interaction in vitro and the formation of the immunocomplex in live cells, inducing a progressive internalization of 37/67 kDa LR and stabilization of PrPC on the cell surface. These data reveal NSC47924 as a useful tool to regulate PrPC and 37/67 kDa LR trafficking and degradation, representing a novel small molecule to be tested against prion diseases.
- Published
- 2016
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