RT Journal Article
SR Electronic
T1 A Proteomic Analysis Reveals the Interaction of GluK1 Ionotropic Kainate Receptor Subunits with Go Proteins
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5171
OP 5179
DO 10.1523/JNEUROSCI.5059-14.2015
VO 35
IS 13
A1 Izabela Rutkowska-Wlodarczyk
A1 M. Isabel Aller
A1 Sergio Valbuena
A1 Jean-Charles Bologna
A1 Laurent Prézeau
A1 Juan Lerma
YR 2015
UL http://www.jneurosci.org/content/35/13/5171.abstract
AB 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.