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Protein S-nitrosylation: a physiological signal for neuronal nitric oxide

Abstract

Nitric oxide (NO) has been linked to numerous physiological and pathophysiological events that are not readily explained by the well established effects of NO on soluble guanylyl cyclase. Exogenous NO S-nitrosylates cysteine residues in proteins, but whether this is an important function of endogenous NO is unclear. Here, using a new proteomic approach, we identify a population of proteins that are endogenously S-nitrosylated, and demonstrate the loss of this modification in mice harbouring a genomic deletion of neuronal NO synthase (nNOS). Targets of NO include metabolic, structural and signalling proteins that may be effectors for neuronally generated NO. These findings establish protein S-nitrosylation as a physiological signalling mechanism for nNOS.

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Figure 1: Detection of S-nitrosylated proteins.
Figure 2: S-nitrosylation of proteins in a brain lysate with GSNO and DEA-NONOate and their identification by mass fingerprinting.
Figure 3: In vitro S-nitrosylation assays identify proteins susceptible to S-nitrosylation.
Figure 4: Endogenous S-nitrosylation is mediated by nNOS.

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Acknowledgements

We thank A. Grewal and A. Nazarian for assistance with mass fingerprinting, A. Kashani for assistance during early stages of this project, and D. Guastella for genotyping the mice. This work was supported by USPHS grants (to S.H.S.), a grant from the National Cancer Institute (to P.T.), a Young Investigator Award from the National Alliance for Research on Schizophrenia and Affective Disorders (to S.R.J.), and a Howard Hughes Fellowship for Physicians (to C.D.F.).

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Correspondence to Solomon H. Snyder.

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Jaffrey, S., Erdjument-Bromage, H., Ferris, C. et al. Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nat Cell Biol 3, 193–197 (2001). https://doi.org/10.1038/35055104

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