Modification and movement: Phosphorylation and SUMOylation regulate endocytosis of GluK2-containing kainate receptors

Kainate receptors (KARs) are tetrameric glutamate-gated ion channels composed of combinations of the subunits GluK1-5. Depending on their precise localization and subunit composition, KARs can regulate neurotransmitter release, synaptic function and neuronal excitability. Because of these diverse roles, the regulated and precisely targeted trafficking of KARs is of crucial importance to neuronal function. We previously reported that the KAR subunit GluK2 is post-translationally modified by attachment of Small Ubiquitin-like Modifier 1 (SUMO-1) and that SUMOylation is required for agonist-dependent endocytosis of GluK2. We recently extended these findings to demonstrate that agonist activation leads to PKC-mediated phosphorylation of GluK2 at serine 868, which directly enhances GluK2 SUMOylation and, in turn, leads to endocytosis of the receptor. These new data demonstrate the importance of interplay between two post-translational modifications in orchestrating the temporal and spatial regulation of kainate receptor trafficking.