Protein SUMOylation modulates calcium influx and glutamate release from presynaptic terminals

Eur J Neurosci. 2009 Apr;29(7):1348-56. doi: 10.1111/j.1460-9568.2009.06692.x.


Posttranslational modification by small ubiquitin-like modifier (SUMO) proteins is emerging as an important regulatory mechanism for neuronal function and dysfunction. Although multiple potential presynaptic SUMOylation substrate proteins have been proposed from sequence analysis the functional consequences of presynaptic SUMOylation have not been determined. Here we show that SUMOylation of presynaptic proteins modulates neurotransmitter release. Increasing protein SUMOylation by entrapping recombinant SUMO-1 in synaptosomes decreased glutamate release evoked by KCl whereas decreasing SUMOylation with the SUMO-specific protease SENP-1 enhanced KCl-evoked release. In contrast, SUMO increased and SENP-1 decreased synaptosomal glutamate release evoked by kainate stimulation. Consistent with these results, SENP-1 increased Ca(2+) influx into synaptosomes evoked by KCl whereas it decreased kainate-induced Ca(2+) influx. These results demonstrate that, in addition to postsynaptic effects, protein SUMOylation acts to modulate neurotransmitter release and thereby regulate synaptic function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Central Nervous System Stimulants / administration & dosage
  • Endopeptidases / metabolism
  • Excitatory Amino Acid Agonists / administration & dosage
  • Glutamic Acid / metabolism*
  • Kainic Acid / administration & dosage
  • Male
  • N-Methylaspartate / administration & dosage
  • Potassium Chloride / administration & dosage
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology*
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / metabolism
  • SUMO-1 Protein / metabolism
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Synaptosomes / drug effects
  • Synaptosomes / physiology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / administration & dosage


  • Central Nervous System Stimulants
  • Excitatory Amino Acid Agonists
  • Recombinant Proteins
  • SUMO-1 Protein
  • Small Ubiquitin-Related Modifier Proteins
  • Glutamic Acid
  • N-Methylaspartate
  • Potassium Chloride
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Endopeptidases
  • Kainic Acid
  • Calcium