title: The prion protein selectively binds to and modulates the content of purinergic receptor P2X4R.
abstract: The GPI-anchored prion protein (PrP(C)) is involved in neurodegeneration, either through misfolding in the Transmissible Spongiform Encephalopathies (TSE), or as a mediator of the neurotoxicity of peptide oligomers in Alzheimer's Disease. PrP(C) has been attributed pleiotropic functions, and appears to scaffold a variety of cell surface signaling modules, for example through its binding to several neurotransmitter receptors. Here we used transfected HEK293 cells to test for an interaction of PrP(C) with purinergic receptor P2X4R. The prion protein bound P2X4R in both overlay and co-immunoprecipitation assays, and co-localized mostly intracellularly, but occasionaly at the cell surface in confocal micrographs. Functional PrP(C):P2X4R interaction was tested by the uptake of a P2X4R-permeant compound, and by modulation of intracellular calcium. Unexpectedly, however, this interaction was traced to a selective effect of PrP(C) upon the content of co-transfected P2X4R. The results suggest a role of PrP(C) in proteostasis, dysfunctions of which may be involved in the pathogenesis of neurodegenerative diseases such as TSE and Alzheimer's Disease.
authors.affiliation: Instituto de Biofísica, UFRJ, Rio de Janeiro, Brazil. Electronic address: mari.vaz.biof@gmail.com.
authors.forename: Mariana V
authors.initials: MV
authors.lastname: Carneiro
authors.affiliation: Instituto de Biofísica, UFRJ, Rio de Janeiro, Brazil. Electronic address: tamerico@biof.ufrj.br.
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Americo
authors.affiliation: Instituto de Ciências Biomédicas, UFRJ, Rio de Janeiro, Brazil. Electronic address: marilia@icb.ufrj.br.
authors.forename: Marilia Z P
authors.initials: MZ
authors.lastname: Guimarães
authors.affiliation: Instituto de Biofísica, UFRJ, Rio de Janeiro, Brazil. Electronic address: rlinden@biof.ufrj.br.
authors.forename: Rafael
authors.initials: R
authors.lastname: Linden
mesh_terms: D000818:Animals; D001665:Binding Sites; D002531:Cerebellum / Q000737:chemistry* / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D018621:PrPC Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D058848:Receptors, Purinergic P2X4 / Q000737:chemistry* / Q000378:metabolism*; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism
chemical_list: D018621:PrPC Proteins; D058848:Receptors, Purinergic P2X4
keywords: Neurodegeneration; Neurotransmission; Prion; Proteostasis; Scaffold protein; Signal transduction