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ADAR2-mediated Q/R editing of GluK2 regulates kainate receptor upscaling in response to suppression of synaptic activity

Research output: Contribution to journalArticle

Original languageEnglish
Article numberjcs222273
Number of pages11
JournalJournal of Cell Science
Volume131
Issue number24
Early online date17 Dec 2018
DOIs
DateAccepted/In press - 19 Nov 2018
DateE-pub ahead of print - 17 Dec 2018
DatePublished (current) - Dec 2018

Abstract

Kainate receptors (KARs) regulate neuronal excitability and network function. Most KARs contain the subunit GluK2 and the properties of these receptors are determined in part by ADAR2-mediated mRNA editing of GluK2 that changes a genomically encoded glutamine (Q) to arginine (R). Suppression of synaptic activity reduces ADAR2-dependent Q/R editing of GluK2 with a consequential increase in GluK2-containing KAR surface expression. However, the mechanism underlying this reduction in GluK2 editing has not been addressed. Here we show that induction of KAR upscaling results in proteasomal degradation of ADAR2, which reduces GluK2 Q/R editing. Because KARs incorporating unedited GluK2(Q) assemble and exit the ER more efficiently this leads to an upscaling of KAR surface expression. Consistent with this, we demonstrate that partial ADAR2 knockdown phenocopies and occludes KAR upscaling. Moreover, we show that although the AMPAR subunit GluA2 also undergoes ADAR2-dependent Q/R editing, this process does not mediate AMPAR upscaling. These data demonstrate that activity-dependent regulation of ADAR2 proteostasis and GluK2 Q/R editing are key determinants of KAR, but not AMPAR, trafficking and upscaling.

    Research areas

  • Synapse, Kainate receptor, AMPA receptor, GluK 2, GluA2, ADAR2, mRNA editing, homeostatic plasticity, scaling

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via the Company of Biologists at http://jcs.biologists.org/content/131/24/jcs222273 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 5 MB, PDF-document

    Embargo ends: 17/12/19

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