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

Nitric oxide (NO) has been linked to numerous physiological and pathophysiological events that ave 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 effecters for neuronally generated PIG. These findings establish protein S-nitrosylation as a physiological signalling mechanism for nNOS.