NR AWLW
AU Petrakis,S.; Irinipoulou,T.; Engelstein,R.; Lindstrom,J.; Orr-Urtreger,A.; Gabizon,R.; Sklaviadis,T.K.
TI Prion protein co-localizes with nicotinic acetylcholine receptor 4 subunit in central nervous system and gastrointestinal tract
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions CE-39
PT Konferenz-Poster
AB PrPc, the cellular isoform of prion protein, is widely expressed in most tissues including brain, muscle and the gastrointestinal tract. Despite its involvement in several bioprocesses such as copper metabolism, neuroprotection and signal transduction, PrP has still no apparent physiological role. During propagation of Transmissible Spongiform Encephalopathies (TSE), prion protein is converted to the pathological isoform, PrPsc, in a process believed to be mediated by as yet unknown host factors. The identification of proteins associated with PrP may provide information about both the biology of prions and the pathogenesis of TSE. So far, PrPc has been shown to interact with synaptic proteins, components of the cytoskeleton and intracellular proteins involved in signalling pathways. Here, we describe the association of PrP with the 4 subunit of nicotinic acetylcholine receptor (nAChR) as indicated by co-immunoprecipitation assays and double-label immunofluorescence. The interaction between prion protein and native 4 subunit was further studied by affinity chromatography, using immobilized and refolded recombinant PrP as a bait and brain homogenates from normal individuals. Additionally, the participation of 4 subunit in the pathogenesis of TSE was studied by in vivo assays. 4-/- mice were challenged with the infectious agent and displayed altered incubation times compared to 4+/+ animals. Our results suggest that PrPc is a member of a multi-protein membrane complex that participates in the formation and stabilization of 34 nAChRs. These receptors may play a role in the uptake of the infectious agent and the pathogenesis of prion diseases.
AD S. Petrakis, Theodoros K. Sklaviadis (sklaviad@auth.gr), Prion Disease Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; T. Irinipoulou: INSERM/Universite Pierre et Marie Curie U536, Institut du Fer a Moulin, 75005 Paris, France; R. Engelstein, R. Gabizon: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassa University Hospital, Jerusalem 91120, Israel; J. Lindstrom: Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA; A. Orr-Urtreger: The Genetics Institute, Tel-Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel
SP englisch
PO Italien