A proteomic analysis reveals the interaction of GluK1 ionotropic kainate receptor subunits with go proteins

Autor: I. Rutkowska-Wlodarczyk, Juan Lerma, Laurent Prézeau, J.-C. Bologna, María Isabel Aller, Sergio Valbuena
Přispěvatelé: European Commission, Ministerio de Ciencia e Innovación (España), Ministerio de Educación y Ciencia (España)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Popis: Kainate receptors (KARs) are found ubiquitously in the CNS and are present presynaptically and postsynaptically regulating synaptic transmission and excitability. Functional studies have proven that KARs act as ion channels as well as potentially activating G-proteins, thus indicating the existance of a dual signaling system for KARs. Nevertheless, it is not clear how these ion channels activate G-proteins and which of the KAR subunits is involved. Here we performed a proteomic analysis to define proteins that interact with the C-terminal domain of GluK1 and we identified a variety of proteins with many different functions, including a Go α subunit. These interactions were verified through distinct in vitro and in vivo assays, and the activation of the Go protein by GluK1 was validated in bioluminescence resonance energy transfer experiments, while the specificity of this association was confirmed in GluK1-deficient mice. These data reveal components of the KAR interactome, and they show that GluK1 and Go proteins are natural partners, accounting for the metabotropic effects of KARs.
This work was supported by grants to J.L. from the Spanish Ministry of Science and Innovation (BFU2006-07138 and BFU2011-24084), CONSOLIDER (CSD2007-00023), and Prometeo/2011/086, and by the EU FP7 Capacities Project BIO-IMAGINE (Grant Agreement No. 264173).
Databáze: OpenAIRE