SUMO1 Affects Synaptic Function, Spine Density and Memory

Sci Rep. 2015 May 29:5:10730. doi: 10.1038/srep10730.


Small ubiquitin-like modifier-1 (SUMO1) plays a number of roles in cellular events and recent evidence has given momentum for its contributions to neuronal development and function. Here, we have generated a SUMO1 transgenic mouse model with exclusive overexpression in neurons in an effort to identify in vivo conjugation targets and the functional consequences of their SUMOylation. A high-expressing line was examined which displayed elevated levels of mono-SUMO1 and increased high molecular weight conjugates in all brain regions. Immunoprecipitation of SUMOylated proteins from total brain extract and proteomic analysis revealed ~95 candidate proteins from a variety of functional classes, including a number of synaptic and cytoskeletal proteins. SUMO1 modification of synaptotagmin-1 was found to be elevated as compared to non-transgenic mice. This observation was associated with an age-dependent reduction in basal synaptic transmission and impaired presynaptic function as shown by altered paired pulse facilitation, as well as a decrease in spine density. The changes in neuronal function and morphology were also associated with a specific impairment in learning and memory while other behavioral features remained unchanged. These findings point to a significant contribution of SUMO1 modification on neuronal function which may have implications for mechanisms involved in mental retardation and neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / growth & development*
  • Brain / metabolism
  • Cells, Cultured
  • Mice
  • Mice, Transgenic
  • Neurons / metabolism*
  • Proteomics*
  • SUMO-1 Protein / genetics*
  • SUMO-1 Protein / metabolism
  • Sumoylation / genetics
  • Synaptic Transmission / genetics
  • Synaptotagmin I / metabolism


  • SUMO-1 Protein
  • Synaptotagmin I
  • Syt1 protein, mouse