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dc.contributor.authorKonopacki, F.A.*
dc.contributor.authorJaafari, N.*
dc.contributor.authorRocca, D.L.*
dc.contributor.authorWilkinson, K.A.*
dc.contributor.authorChamberlain, S.E.*
dc.contributor.authorRubin, P.*
dc.contributor.authorKantamneni, Sriharsha*
dc.contributor.authorMellor, J.R.*
dc.contributor.authorHenley, J.M.*
dc.date.accessioned2014-04-28T10:52:19Z
dc.date.available2014-04-28T10:52:19Z
dc.date.issued2011
dc.identifier.citationKonopacki FA, Jaafari N, Rocca DL et al (2011) Agonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis. Proceedings of the National Academy of Sciences of the United States of America. 108(49): 19772-19777.
dc.identifier.urihttp://hdl.handle.net/10454/6054
dc.descriptionNo
dc.description.abstractThe surface expression and regulated endocytosis of kainate (KA) receptors (KARs) plays a critical role in neuronal function. PKC can modulate KAR trafficking, but the sites of action and molecular consequences have not been fully characterized. Small ubiquitin-like modifier (SUMO) modification of the KAR subunit GluK2 mediates agonist-evoked internalization, but how KAR activation leads to GluK2 SUMOylation is unclear. Here we show that KA stimulation causes rapid phosphorylation of GluK2 by PKC, and that PKC activation increases 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 KA. Phosphomimetic mutagenesis of S868 increased GluK2 SUMOylation, and mutation of S868 to a nonphosphorylatable alanine prevented KA-induced SUMOylation and endocytosis in neurons. Infusion of SUMO-1 dramatically reduced KAR-mediated currents in HEK293 cells expressing WT GluK2 or nonphosphorylatable S846A mutant, but had no effect on currents mediated by the S868A mutant. 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 in regulating the surface expression and function of GluK2-containing KARs.
dc.relation.isreferencedbyhttp://dx.doi.org/10.1073/pnas.1111575108
dc.subjectAlanine
dc.subject; Amino acid substitution
dc.subject; Animals
dc.subject; Blotting; Western
dc.subject; COS cells
dc.subject; Cercopithecus aethiops
dc.subject; Endocytosis
dc.subject; HEK293 cells
dc.subject; Humans
dc.subject; Kainic acid
dc.subject; Luminescent proteins
dc.subject; Microscopy
dc.subject; Mutation
dc.subject; Neurons
dc.subject; Phosphorylation
dc.subject; Protein kinase C
dc.subject; Rats
dc.subject; Wistar
dc.subject; Receptors
dc.subject; SUMO-1 Protein
dc.subject; Serine
dc.subject; Sumoylation
dc.subject; REF 2014
dc.titleAgonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis
dc.status.refereedYes
dc.typeArticle
dc.type.versionNo full-text in the repository


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