Synaptic localization of the SUMOylation-regulating protease SENP5 in the adult mouse brain

Hiroki Akiyama, Kazuhiko Nakadate, Shin Ichi Sakakibara*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Covalent conjugation of small ubiquitin-like modifiers (SUMOs) or SUMOylation is a reversible post-translational modification that regulates the stability and function of target proteins. SUMOs are removed from substrate proteins by sentrin/SUMO-specific proteases (SENPs). Numerous studies have implicated SUMOylation in various physiological and pathological processes in neurons. To understand the functional roles of SUMOylation, it is necessary to determine the distribution of enzymes regulating SUMO conjugation and deconjugation; yet, the localization of SENPs has not been described in detail in intact brain tissue. Here, we report the distribution and subcellular localization of SENP3 and 5 in the adult murine brain. Immunohistochemical analyses revealed the ubiquitous distribution of both SENPs across different brain regions. Within individual cells, SENP3 was confined to the nucleus, consistent with the conventional view that SENPs regulate nuclear events. In contrast, SENP5 was detected in the neuropil but not in cell bodies. Moreover, strong SENP5 immunoreactivity was observed in regions with high numbers of synapses such as the cerebellar glomeruli, suggesting that SENP5 localizes to pre- and/or postsynaptic structures. We performed double immunolabeling in cultured neurons and found that SENP5 co-localized with pre- and post-synaptic markers, as well as a mitochondrial marker. Immunoelectron microscopy confirmed this finding and revealed that SENP5 was localized to presynaptic terminals, postsynaptic spines, and mitochondria in axon terminals. These findings advance the current understanding of the functional roles of SUMOylation in neurons, especially in synaptic regulation, and have implications for future therapeutic strategies in neurodegenerative disorders mediated by mitochondrial dysfunction.

Original languageEnglish
Pages (from-to)990-1005
Number of pages16
JournalJournal of Comparative Neurology
Issue number6
Publication statusPublished - 2018 Apr 15


  • RRID: AB_10598496
  • RRID: AB_10643377
  • RRID: AB_10694546
  • RRID: AB_1843992
  • RRID: AB_1950371
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  • RRID: AB_2313606
  • RRID: AB_2336171
  • RRID: AB_2687591
  • RRID: AB_303248
  • RRID: AB_592786
  • RRID: AB_772211
  • sentrin/SUMO-specific protease
  • small ubiquitin-like modifier
  • synapse

ASJC Scopus subject areas

  • General Neuroscience


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