Kainate receptors (KARs) are glutamate receptors that are built from multimeric assemblies of GluK1–GluK5 subunits. RNA editing mediated by the nuclear enzyme ADAR2, which edits GluK2, adds to the diversity of these receptors, changing a genomically encoded glutamine residue (Q) to an arginine residue (R). ADAR2-dependent Q/R editing of GluK2 can be reduced by suppression of synaptic activity, which increases surface expression of GluK2-containing KARs as a consequence (KAR upscaling or homeostatic plasticity). The mechanisms involved in reducing Q/R editing, however, are unknown. Here, Jeremy Henley and colleagues (Gurung et al., 2018) investigate the molecular and cellular mechanisms that lead to GluK2-containing KAR upscaling. The authors show that treatment with the neurotoxin TTX, a well-established protocol for inducing AMPAR scaling, leads to upscaling of the KARs by promoting the proteasomal degradation of ADAR2. GluK2 pre-mRNA Q/R editing is reduced when levels of ADAR2 are decreased, and because KARs that incorporate unedited GluK2(Q) assemble and exit the ER more efficiently, GluK2-containing KAR surface expression is enhanced. The authors then demonstrate that partial knockdown of ADAR2 is sufficient to upscale KARs, mimicking TTX-evoked KAR upscaling, and also occludes any further TTX-mediated upscaling. These data provide valuable insight into the mechanisms underlying homeostatic plasticity, and add to our understanding of how KAR regulation can control neuron excitability and network activity.
ADAR2-mediated mRNA editing underpins KAR homeostatic plasticity
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ADAR2-mediated mRNA editing underpins KAR homeostatic plasticity. J Cell Sci 15 December 2018; 131 (24): e2403. doi:
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