SummaryPhosphorylation or SUMOylation of the kainate receptor (KAR) subunit GluK2 have both individually been shown to regulate KAR surface expression. However, it is unknown if phosphorylation and SUMOylation of GluK2 are important for activity-dependent KAR synaptic plasticity. Here, we show that PKC-mediated phosphorylation of GluK2 at serine 868 promotes GluK2 SUMOylation at lysine 886 and that both these events are necessary for the internalization of GluK2 containing KARs that occurs during long-term depression of KAR-mediated synaptic transmission at rat hippocampal mossy fiber synapses. Conversely, phosphorylation of GluK2 at serine 868 in the absence of SUMOylation leads to an increase in KAR surface expression by facilitating receptor recycling between endosomal compartments and the plasma membrane. Thus, we describe a role for the dynamic control of synaptic SUMOylation in the regulation of KAR synaptic transmission and plasticity.

Background:The glutamate transporter GLT-1 is regulated by PKC, which promotes its ubiquitination and subsequent endocytosis. Results: Phosphorylation of GLT-1 occurs at Ser-520, whereas ubiquitination is mediated by the ubiquitin ligase Nedd4-2. Conclusion: PKC-promoted endocytosis of GLT-1 requires Nedd4-2-dependent ubiquitination but not its phosphorylation. Significance: Intracellular trafficking of glutamate transporters seems to play a major role in the pathophysiology of the nervous system.