Kainate receptor activation induces glycine receptor endocytosis through PKC deSUMOylation

Nat Commun. 2014 Sep 19;5:4980. doi: 10.1038/ncomms5980.

Abstract

Surface expression and regulated endocytosis of glycine receptors (GlyRs) play a critical function in balancing neuronal excitability. SUMOylation (SUMO modification) is of critical importance for maintaining neuronal function in the central nervous system. Here we show that activation of kainate receptors (KARs) causes GlyR endocytosis in a calcium- and protein kinase C (PKC)-dependent manner, leading to reduced GlyR-mediated synaptic activity in cultured spinal cord neurons and the superficial dorsal horn of rat spinal cord slices. This effect requires SUMO1/sentrin-specific peptidase 1 (SENP1)-mediated deSUMOylation of PKC, indicating that the crosstalk between KARs and GlyRs relies on the SUMOylation status of PKC. SENP1-mediated deSUMOylation of PKC is involved in the kainate-induced GlyR endocytosis and thus plays an important role in the anti-homeostatic regulation between excitatory and inhibitory ligand-gated ion channels. Altogether, we have identified a SUMOylation-dependent regulatory pathway for GlyR endocytosis, which may have important physiological implications for proper neuronal excitability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotinylation
  • Calcium / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Endocytosis*
  • Endopeptidases / metabolism
  • Endosomes / metabolism
  • Female
  • Homeostasis
  • Kainic Acid / chemistry
  • Ligands
  • Male
  • Neurons / metabolism
  • Neurotransmitter Agents / metabolism
  • Patch-Clamp Techniques
  • Protein Kinase C / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glycine / metabolism*
  • Receptors, Kainic Acid / metabolism*
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Spinal Cord / metabolism

Substances

  • Ligands
  • Neurotransmitter Agents
  • Receptors, Glycine
  • Receptors, Kainic Acid
  • Small Ubiquitin-Related Modifier Proteins
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Endopeptidases
  • SENP1 protein, rat
  • Kainic Acid
  • Calcium