RT Journal Article
SR Electronic
T1 ADAR2 mediated Q/R editing of GluK2 regulates homeostatic plasticity of kainate receptors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 308650
DO 10.1101/308650
A1 Sonam Gurung
A1 Ashley J. Evans
A1 Kevin A. Wilkinson
A1 Jeremy M. Henley
YR 2018
UL http://biorxiv.org/content/early/2018/04/25/308650.abstract
AB Kainate receptors (KARs) are heteromeric glutamate-gated ion channels that regulate neuronal excitability and network function in the brain. Most KARs contain the subunit GluK2 and the precise properties of these GluK2-containing KARs are determined by additional factors including ADAR2-mediated mRNA editing of a single codon that changes a genomically encoded glutamine (Q) to arginine (R) in the pore-lining region of GluK2. ADAR2-dependent Q/R editing of GluK2 is dynamically regulated during homeostatic plasticity (scaling) elicited by suppression of synaptic activity with TTX. Here we show that TTX decreases levels of ADAR2 by enhancing its proteasomal degradation. This selectively reduces the numbers of GluK2 subunits that are edited and increases the surface expression of GluK2-containing KARs. Furthermore, we show that partial ADAR2 knockdown phenocopies and occludes TTX-induced scaling of KARs. These data indicate that activity-dependent regulation of ADAR2 proteostasis and GluK2 Q/R editing provides a mechanism for KAR homeostatic plasticity.