Smith, JG;
Aldous, SG;
Andreassi, C;
Cuda, G;
Gaspari, M;
Riccio, A;
(2018)
Proteomic analysis of S-nitrosylated nuclear proteins in rat cortical neurons.
Science Signaling
, 11
(537)
, Article eaar3396. 10.1126/scisignal.aar3396.
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Abstract
The ability of neurons to modulate gene expression in response to extrinsic signals is necessary for proper brain function. S-nitrosylation is the covalent attachment of a nitric oxide (NO) moiety to cysteine thiols and is critical for transducing extracellular stimuli into specific patterns of gene expression. In the cerebral cortex, S-nitrosylation of histone deacetylase 2 (HDAC2) is required for gene transcription during neuronal development, however only few nuclear targets of Snitrosylation have been identified to date. Here, we used S-nitrosothiol Resin Assisted Capture (SNORAC) coupled with mass spectrometry analysis to identify 614 S-nitrosylated nuclear proteins. Of these, 131 proteins had never been shown to be S-nitrosylated in any system, and 612 are new targets of S-nitrosylation in neurons. The site(s) of S-nitrosylation were identified for 59% of the targets, and motifs containing single lysines found at 33% of these sites. In addition, lysine motifs were found to be necessary for promoting S-nitrosylation of HDAC2 and Methyl-CpG Binding Protein 3 (MBD3). Moreover, S-nitrosylation of the histone binding protein RBBP7 was found to be necessary for dendritogenesis. Overall, our study provides the first extensive characterization of Snitrosylated nuclear proteins in neurons and identifies putative S-nitrosylation motifs that may be shared with other targets of nitric oxide signaling.
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