Interaction between the cellular prion (PrPC) and the 2P domain K+ channel TREK-1 protein.
The cellular prion protein (PrP(C)) is a highly conserved protein throughout the evolution of mammals and therefore is thought to play important cellular functions. Despite decades of intensive researches, the physiological function of PrP(C) remains enigmatic. Differently, in particular pathological contexts, generally referred as transmissible spongiform encephalopathies, a conformational isoform of PrP(C), i.e., PrP(Sc), is considered the causative agent of these diseases. In this study, we investigated putative PrP(C) cellular functions through the identification of PrP(C) protein interactants. Using a bacterial two-hybrid approach, we identified a novel interaction between PrP(C) and a two-pore potassium channel protein, TREK-1. This interaction was further verified in transfected eukaryotic cells using co-immunoprecipitation and confocal microscopic analysis of the fluorescent transfected proteins. Importantly, in the cerebellar cortex, the endogenous PrP(C) and TREK-1 proteins exhibited co-localization signals in correspondence of the Purkinje cells. Furthermore, a deletion mapping study defined the carboxyl-terminal regions of the two proteins as the possible determinants of the PrP(C)-TREK-1 interaction. Our results indicated a novel PrP(C) interacting protein and suggested that this complex might be relevant in modulating a variety of electrophysiological-dependent cellular responses.
Azzalin
Alberto
A
Dipartimento di Genetica e Microbiologia, Università di Pavia, Pavia, Italy.
Ferrara
Valentina
V
Arias
Agustina
A
Cerri
Silvia
S
Avella
Debora
D
Pisu
Maria Bonaria
MB
Nano
Rosanna
R
Bernocchi
Graziella
G
Ferretti
Luca
L
Comincini
Sergio
S
D000818:Animals; D002525:Cerebellar Cortex / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D018621:PrPC Proteins / Q000378:metabolism*; D025941:Protein Interaction Mapping; D051381:Rats; D020798:Two-Hybrid System Techniques
D024683:Potassium Channels, Tandem Pore Domain; D018621:PrPC Proteins; C103742:potassium channel protein TREK-1