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bioRxiv · 10.1101/2022.10.31.514576

GluK2 Q/R editing regulates kainate receptor signalling and synaptic AMPA receptor expression and function.

Nair, J.·Wilkinson, K.·Mulle, C.·Vissel, B.·MELLOR, J.·Henley, J.
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Abstract

Q/R editing of the kainate receptor (KAR) subunit GluK2 radically alters properties of recombinant KARs, but the effects in vivo remain largely unexplored. We compared GluK2 editing-deficient mice that express [~]95% unedited GluK2(Q) to wild-type counterparts that express [~]85% edited GluK2(R). At mossy fibre-CA3 (MF-CA3) synapses GluK2(Q) mice displayed enhanced postsynaptic KAR function and increased KAR-mediated presynaptic facilitation, demonstrating heightened ionotropic function. Conversely, there was reduced metabotropic KAR function, assessed by KAR-mediated afterhyperpolarization currents, in GluK2(Q) mice. GluK2(Q) mice 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 signalling to regulate synaptic expression of AMPARs and plasticity.

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Nair, J., Wilkinson, K., Mulle, C., Vissel, B., MELLOR, J., Henley, J.. 2022-11-01. GluK2 Q/R editing regulates kainate receptor signalling and synaptic AMPA receptor expression and function.. https://doi.org/10.1101/2022.10.31.514576

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