Nitric oxide (NO) is a second messenger generated by the action of nitric oxide synthase (NOS). NO is a highly reactive gas, and Fang et al. studied how cells control this reactivity to direct NO to react with the desired target protein to transmit the proper signal. The protein CAPON, which can interact with neuronal NOS (nNOS), bound to Dexras1 in a yeast two-hybrid screen. Dexras1 is a member of the Rap subfamily of the small guanosine triphosphatase Ras family. In glutathione S-transferase pull-down and coimmunoprecipitation experiments, Dexras1 and nNOS were found to interact indirectly through CAPON, thus, CAPON is an adaptor for nNOS and Dexras1. Dexras1 can be directly nitrosylated and nitrosylation stimulates Dexras1 activity. In vivo, the stimulation of Dexras1 activity by a pathway dependent on the NMDA glutamate receptor can be inhibited by NOS inhibitors, and Dexras1 activity is decreased in nNOS-/- mice. The importance of CAPON in mediating the nNOS and Dexras1 interaction was demonstrated in cotransfection experiments in which only when CAPON was transfected with nNOS and Dexras1 was Dexras1 activity stimulated. Direct nitrosylation of proteins is an emerging mechanism of regulation, and the identification of CAPON demonstrates one way for cells to control and target nitrosylation to the proper downstream partners.
Fang, M., Jaffrey, S.R., Sawa, A., Ye, K., Luo, X., and Snyder, S.H. (2000) Dexras1: A G protein specifically coupled to neuronal nitric oxide synthase via CAPON. Neuron 28: 183-193. [Online Journal]