Cellular prion protein co-localizes with nAChR beta4 subunit in brain and gastrointestinal tract.
PrP(C), the cellular isoform of prion protein, is widely expressed in most tissues, including brain, muscle and gastrointestinal tract. Despite its involvement in several bioprocesses, PrP has still no apparent physiological role. During propagation of transmissible spongiform encephalopathies (TSE), prion protein is converted to the pathological isoform, PrP(Sc), in a process believed to be mediated by unknown host factors. The identification of proteins associated with PrP may provide information about both the biology of prions and the pathogenesis of TSE. Thus far, PrP(C) 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 beta4 subunit of nicotinic acetylcholine receptor (nAChR), as indicated by co-immunoprecipitation assays and double-label immunofluorescence. The interaction between prion protein and native beta4 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 beta4 subunit in the pathogenesis of TSE was studied by in vivo assays. beta4(-/-) and wild-type mice were challenged with the RML (Rocky Mountain Laboratories) infectious agent. Transgenic animals displayed altered incubation times but the deletion of beta4 subunit did not result in a significant change of the incubation period of the disease. Our results suggest that PrP(C) is a member of a multiprotein membrane complex participating in the formation and function of alpha3beta4 nAChR.
Petrakis
S
S
Prion Disease Research Group, Laboratory of Pharmacology, School of Pharmaceutical Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Irinopoulou
T
T
Panagiotidis
C H
CH
Engelstein
R
R
Lindstrom
J
J
Orr-Urtreger
A
A
Gabizon
R
R
Grigoriadis
N
N
Sklaviadis
T
T
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005455:Fluorescent Antibody Technique; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018621:PrPC Proteins / Q000378:metabolism*; D018620:PrPSc Proteins / Q000472:pathogenicity; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012756:Sheep; D013347:Subcellular Fractions
C486720:Chrnb4 protein, mouse; D009419:Nerve Tissue Proteins; D018621:PrPC Proteins; D018620:PrPSc Proteins; D021122:Protein Subunits; D011978:Receptors, Nicotinic