Projects per year
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.
Original language | English |
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Article number | jcs222273 |
Number of pages | 11 |
Journal | Journal of Cell Science |
Volume | 131 |
Issue number | 24 |
Early online date | 17 Dec 2018 |
DOIs | |
Publication status | Published - Dec 2018 |
Keywords
- Synapse
- Kainate receptor
- AMPA receptor
- GluK 2
- GluA2
- ADAR2
- mRNA editing
- homeostatic plasticity
- scaling
Fingerprint
Dive into the research topics of 'ADAR2-mediated Q/R editing of GluK2 regulates kainate receptor upscaling in response to suppression of synaptic activity'. Together they form a unique fingerprint.Projects
- 2 Finished
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Mechanisms and consequences of presynaptic protein SUMOylation in the regulation of neurotransmitter release
Henley, J. M. (Principal Investigator)
31/12/13 → 29/04/17
Project: Research
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PROTEIN INTERACTIONS AND POST TRANSATIONAL MODIFICATION IN THE TRAFFICKING OF NEURONAL KAINATE RECEPTORS
Henley, J. M. (Principal Investigator)
1/01/08 → 1/10/11
Project: Research
Profiles
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Emeritus Professor Jeremy M Henley
- School of Biochemistry - Emeritus Professor
- Dynamic Cell Biology
- Bristol Neuroscience
Person: Member, Honorary and Visiting Academic