Dexras1: A G protein specifically coupled to neuronal nitric oxide synthase via CAPON

Because nitric oxide (NO) is a highly reactive signaling molecule, chemical inactivation by reaction with oxygen, superoxide, and glutathione competes with specific interactions with target proteins. NO signaling may be enhan ced by adaptor proteins that couple neuronal NO synthase (nNOS) to specific target proteins. Here we identify a selective interaction of the nNOS adap tor protein CAPON with Dexras1, a brain-enriched member of the Pas family o f small monomeric G proteins. We find that Dexras1 is activated by NO donor s as well as by NMDA receptor-stimulated NO synthesis in cortical neurons. The importance of Dexras1 as a physiologic target of nNOS is established by the selective decrease of Dexras1 activation, but not H-Ras or four other Pas family members, in the brains of mice harboring a targeted genomic dele tion of nNOS (nNOS(-/-)). We also find that nNOS, CAPON, and Dexras1 form a ternary complex that enhances the ability of nNOS to activate Dexras1. The se findings identity Dexras1 as a novel physiologic NO effector and suggest that anchoring of nNOS to specific targets is a mechanism by which NO sign aling is enhanced.