Interaction between the cellular prion (PrP C) and the 2P domain K + channel TREK-1 protein

Abstract

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.