Agonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis

F.A Konopacki, N Jaafari, D Rocca, K.A Wilkinson, S.E.L Chamberlain, P Rubin, S Kantamneni, J.R Mellor, JM Henley

Research output: Contribution to journalArticle (Academic Journal)peer-review

51 Citations (Scopus)


The surface expression and regulated endocytosis of kainate receptors (KARs) plays a critical role in neuronal function. Protein kinase C (PKC) can modulate KAR trafficking but the sites of action and molecular consequences have not been fully characterised. SUMO modification of the KAR subunit GluK2 mediates agonist-invoked internalisation but how KAR activation leads to GluK2 SUMOylation is unclear. Here we show that kainate (KA) stimulation causes rapid phosphorylation of GluK2 by PKC. Further, PKC activation increased GluK2 SUMOylation both in vitro and in neurons. The intracellular C-terminal domain of GluK2 contains two predicted PKC phosphorylation sites, S846 and S868 both of which are phosphorylated in response to kainate. Phosphomimetic mutagenesis of S868 increased GluK2 SUMOylation and mutation of S868 to a non-phosphorylatable alanine prevented KA-induced SUMOylation and endocytosis in neurons. Infusion of SUMO-1 dramatically reduced KAR-mediated currents in HEK293 cells expressing wild type GluK2 or non-phosphorylatable S846A mutant, whereas currents mediated by the S868A mutant were unaffected by SUMO-1. These data demonstrate that agonist activation of GluK2 promotes PKC-dependent phosphorylation of S846 and S868 but that only S868 phosphorylation is required to enhance GluK2 SUMOylation and promote endocytosis. Thus, direct phosphorylation by PKC and GluK2 SUMOylation are intimately linked to regulate the surface expression and function of GluK2-containing KARs.
Translated title of the contributionAgonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis
Original languageEnglish
Pages (from-to)19772 - 19777
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number49
Publication statusPublished - Dec 2011

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