SUMOylation is required for glycine-induced increases in AMPA receptor surface expression (ChemLTP) in hippocampal neurons

PLoS One. 2013;8(1):e52345. doi: 10.1371/journal.pone.0052345. Epub 2013 Jan 11.


Multiple pathways participate in the AMPA receptor trafficking that underlies long-term potentiation (LTP) of synaptic transmission. Here we demonstrate that protein SUMOylation is required for insertion of the GluA1 AMPAR subunit following transient glycine-evoked increase in AMPA receptor surface expression (ChemLTP) in dispersed neuronal cultures. ChemLTP increases co-localisation of SUMO-1 and the SUMO conjugating enzyme Ubc9 and with PSD95 consistent with the recruitment of SUMOylated proteins to dendritic spines. In addition, we show that ChemLTP increases dendritic levels of SUMO-1 and Ubc9 mRNA. Consistent with activity dependent translocation of these mRNAs to sites near synapses, levels of the mRNA binding and dendritic transport protein CPEB are also increased by ChemLTP. Importantly, reducing the extent of substrate protein SUMOylation by overexpressing the deSUMOylating enzyme SENP-1 or inhibiting SUMOylation by expressing dominant negative Ubc9 prevent the ChemLTP-induced increase in both AMPAR surface expression and dendritic SUMO-1 mRNA. Taken together these data demonstrate that SUMOylation of synaptic protein(s) involved in AMPA receptor trafficking is necessary for activity-dependent increases in AMPAR surface expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cysteine Endopeptidases
  • Dendritic Spines / drug effects*
  • Dendritic Spines / metabolism
  • Dendritic Spines / physiology
  • Disks Large Homolog 4 Protein
  • Endopeptidases / genetics
  • Endopeptidases / metabolism
  • Glycine / pharmacology*
  • Hippocampus / cytology
  • Hippocampus / physiology
  • Immunoblotting
  • In Situ Hybridization, Fluorescence
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microscopy, Confocal
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / physiology
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, AMPA / metabolism
  • Receptors, AMPA / physiology*
  • SUMO-1 Protein / genetics
  • SUMO-1 Protein / metabolism
  • Sumoylation
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism


  • CPEB1 protein, rat
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptors, AMPA
  • SUMO-1 Protein
  • Ubiquitin-Conjugating Enzymes
  • Endopeptidases
  • Cysteine Endopeptidases
  • SENP1 protein, rat
  • ubiquitin-conjugating enzyme UBC9
  • Glycine