GluK2 Q/R editing regulates kainate receptor signaling and long-term potentiation of AMPA receptors
Jithin D. Nair,
Kevin A. Wilkinson,
Busra P. Yucel,
Christophe Mulle,
Bryce Vissel,
Jack Mellor,
Jeremy M. Henley
Affiliations
Jithin D. Nair
Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK
Kevin A. Wilkinson
Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK
Busra P. Yucel
Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK
Christophe Mulle
CNRS UMR 5297, Interdisciplinary Institute of Neuroscience, University of Bordeaux, France
Bryce Vissel
Centre for Neuroscience and Regenerative Medicine, St Vincent’s Hospital, Sydney, NSW, Australia
Jack Mellor
Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK; Corresponding author
Jeremy M. Henley
Centre for Synaptic Plasticity, School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK; Corresponding author
Summary: Q/R editing of the kainate receptor (KAR) subunit GluK2 radically alters recombinant KAR properties, but the effects on endogenous KARs in vivo remain largely unexplored. Here, we compared GluK2 editing-deficient mice that express ∼95% unedited GluK2(Q) to wild-type counterparts that express ∼85% edited GluK2(R). At mossy fiber-CA3 (MF-CA3) synapses GluK2(Q) mice displayed increased postsynaptic KAR function and KAR-mediated presynaptic facilitation, demonstrating enhanced ionotropic function. Conversely, GluK2(Q) mice exhibited reduced metabotropic KAR function, assessed by KAR-mediated inhibition of slow after-hyperpolarization currents (ISAHP). GluK2(Q) mice also had fewer GluA1-and GluA3-containing AMPA receptors (AMPARs) and reduced postsynaptic AMPAR currents at both MF-CA3 and CA1-Schaffer collateral synapses. Moreover, long-term potentiation of AMPAR-mediated transmission at CA1-Schaffer collateral synapses was reduced in GluK2(Q) mice. These findings suggest that GluK2 Q/R editing influences ionotropic/metabotropic balance of KAR signaling to regulate synaptic expression of AMPARs and plasticity.
