GluK2 Q/R editing regulates kainate receptor signaling and long-term potentiation of AMPA receptors

Jithin D Nair, Kevin A Wilkinson, Bushra P Yucel, Christophe Mulle, Bryce Vissel , Jack R Mellor*, Jeremy M Henley*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

1 Citation (Scopus)

Abstract

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.
Original languageEnglish
Article number107708
JournaliScience
Volume26
Issue number10
Early online date24 Aug 2023
DOIs
Publication statusPublished - 20 Oct 2023

Bibliographical note

Funding Information:
This work was supported by the BBSRC (BB/R00787X/1), the Leverhulme Trust (RPG-2019-191) and the Wellcome Trust (105384/Z/14/A). We are grateful to Prof. Susumu Tomita (Yale, USA) for the kind gift of NETO antibody. The graphical abstract and cartoon was made using Biorender.com. Conceptualization, J.D.N. K.A.W. J.M. and J.M.H. Methodology, J.D.N. K.A.W. J.M. and C.M. Investigation, J.D.N. B.P.Y. and K.A.W. Writing, J.D.N. K.A.W. J.M. C.M. and J.M.H. Original Draft and Writing, J.D.N. K.A.W. J.M. and J.M.H. Review and Editing, All authors. Funding Acquisition, J.M.H. Resources, B.V. Supervision, J.M.H. K.A.W. and J.R.M. The authors declare no competing interests.

Funding Information:
This work was supported by the BBSRC ( BB/R00787X/1 ), the Leverhulme Trust ( RPG-2019-191 ) and the Wellcome Trust ( 105384/Z/14/A ). We are grateful to Prof. Susumu Tomita (Yale, USA) for the kind gift of NETO antibody. The graphical abstract and cartoon was made using Biorender.com.

Publisher Copyright:
© 2023 The Authors

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