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SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity

Nature Neuroscience volume 15, pages 845852 (2012) | Download Citation

Abstract

Phosphorylation or SUMOylation of the kainate receptor (KAR) subunit GluK2 have both individually been shown to regulate KAR surface expression. However, it is unknown whether phosphorylation and SUMOylation of GluK2 are important for activity-dependent KAR synaptic plasticity. We found that protein kinase C–mediated phosphorylation of GluK2 at serine 868 promotes GluK2 SUMOylation at lysine 886 and that both of 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 led to an increase in KAR surface expression by facilitating receptor recycling between endosomal compartments and the plasma membrane. Our results suggest a role for the dynamic control of synaptic SUMOylation in the regulation of KAR synaptic transmission and plasticity.

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Acknowledgements

We thank A. Randall for providing electrophysiological facilities for experiments on cultured preparations, and S. Martin and J. Hanley for comments on previous versions of the manuscript. This work was funded by Biotechnology and Biological Sciences Research Council (S.E.L.C., J.R.M. and J.M.H.), the European Research Council (J.A.W. and J.M.H.), Medical Research Council (F.A.K., S.K. and J.M.H.) and the Wellcome Trust (J.R.M., J.M.H.). I.M.G.-G. is a European Molecular Biology Organization Fellow.

Author information

Author notes

    • Sophie E L Chamberlain
    •  & Inmaculada M González-González

    These authors contributed equally to this work.

    • Jeremy M Henley
    •  & Jack R Mellor

    These authors jointly directed this work.

Affiliations

  1. School of Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, University of Bristol, Bristol, UK.

    • Sophie E L Chamberlain
    •  & Jack R Mellor
  2. School of Biochemistry, Medical Research Council Centre for Synaptic Plasticity, University of Bristol, Bristol, UK.

    • Inmaculada M González-González
    • , Kevin A Wilkinson
    • , Filip A Konopacki
    • , Sriharsha Kantamneni
    •  & Jeremy M Henley

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Contributions

S.E.L.C. performed the electrophysiology experiments and analyzed the results. I.M.G.-G. performed the imaging experiments and analyzed the results. K.A.W. and F.A.K. performed the biochemical experiments and analyzed the results. S.K. prepared SUMO and SENP proteins for electrophysiological experiments. J.M.H. and J.R.M. supervised the project. S.E.L.C., I.M.G.-G., J.M.H. and J.R.M. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jack R Mellor.

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DOI

https://doi.org/10.1038/nn.3089

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