Proteomic analysis of S-nitrosylated nuclear proteins in rat cortical neurons

Sci Signal. 2018 Jul 3;11(537):eaar3396. doi: 10.1126/scisignal.aar3396.


Neurons modulate gene expression in response to extrinsic signals to enable brain development, cognition, and learning and to process stimuli that regulate systemic physiological functions. This signal-to-gene communication is facilitated by posttranslational modifications such as S-nitrosylation, the covalent attachment of a nitric oxide (NO) moiety to cysteine thiols. In the cerebral cortex, S-nitrosylation of histone deacetylase 2 (HDAC2) is required for gene transcription during neuronal development, but few other nuclear targets of S-nitrosylation have been identified to date. We used S-nitrosothiol resin-assisted capture on NO donor-treated nuclear extracts from rat cortical neurons and identified 614 S-nitrosylated nuclear proteins. Of these, 131 proteins have not previously been shown to be S-nitrosylated in any system, and 555 are previously unidentified targets of S-nitrosylation in neurons. The sites of S-nitrosylation were identified for 59% of the targets, and motifs containing single lysines were found at 33% of these sites. In addition, lysine motifs were necessary for promoting the S-nitrosylation of HDAC2 and methyl-CpG binding protein 3 (MBD3). Moreover, S-nitrosylation of the histone-binding protein RBBP7 was necessary for dendritogenesis of cortical neurons in culture. Together, our findings characterize S-nitrosylated nuclear proteins in neurons and identify S-nitrosylation motifs that may be shared with other targets of NO signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism*
  • Dendrites / physiology*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Female
  • Neurons / cytology
  • Neurons / metabolism*
  • Nitric Oxide / metabolism*
  • Nuclear Proteins / metabolism*
  • Pregnancy
  • Protein Processing, Post-Translational*
  • Proteome / analysis*
  • Rats
  • Rats, Sprague-Dawley


  • Nuclear Proteins
  • Proteome
  • Nitric Oxide