Distinct functions of kainate receptors in the brain are determined by the auxiliary subunit Neto1
Open Access
- 29 May 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 14 (7), 866-873
- https://doi.org/10.1038/nn.2837
Abstract
Of the three major types of ionotropic glutamate receptors, synaptic kainite receptors have slow channel kinetics. This study characterizes Neto1, a novel auxiliary subunit of kainite receptor that directly modulates ligand binding and slow kinetics of kainite receptors. Ionotropic glutamate receptors principally mediate fast excitatory transmission in the brain. Among the three classes of ionotropic glutamate receptors, kainate receptors (KARs) have a unique brain distribution, which has been historically defined by 3H-radiolabeled kainate binding. Compared with recombinant KARs expressed in heterologous cells, synaptic KARs exhibit characteristically slow rise-time and decay kinetics. However, the mechanisms responsible for these distinct KAR properties remain unclear. We found that both the high-affinity binding pattern in the mouse brain and the channel properties of native KARs are determined by the KAR auxiliary subunit Neto1. Through modulation of agonist binding affinity and off-kinetics of KARs, but not trafficking of KARs, Neto1 determined both the KAR high-affinity binding pattern and the distinctively slow kinetics of postsynaptic KARs. By regulating KAR excitatory postsynaptic current kinetics, Neto1 can control synaptic temporal summation, spike generation and fidelity.Keywords
This publication has 50 references indexed in Scilit:
- Kainate receptors coming of age: milestones of two decades of researchTrends in Neurosciences, 2011
- Glutamate Receptor Ion Channels: Structure, Regulation, and FunctionPharmacological Reviews, 2010
- Subunit-specific desensitization of heteromeric kainate receptorsThe Journal of Physiology, 2010
- High-Affinity Kainate Receptor Subunits Are Necessary for Ionotropic but Not Metabotropic SignalingNeuron, 2009
- Neto1 Is a Novel CUB-Domain NMDA Receptor–Interacting Protein Required for Synaptic Plasticity and LearningPLoS Biology, 2009
- A Transmembrane Accessory Subunit that Modulates Kainate-Type Glutamate ReceptorsNeuron, 2009
- Subunit-Dependent Postsynaptic Expression of Kainate Receptors on Hippocampal Interneurons in Area CA1Journal of Neuroscience, 2009
- Kainate receptors: Pharmacology, function and therapeutic potentialNeuropharmacology, 2008
- KRIP6: A novel BTB/kelch protein regulating function of kainate receptorsMolecular and Cellular Neuroscience, 2007
- Glutamate Receptor GatingCritical Reviews™ in Neurobiology, 2004