Neuronal (nNOS)

Neuronal Nitric Oxide Synthase (nNOS)

Three isoforms of nitric oxide synthase (NOS) have been identified. All are homodimers with subunits of 130-160 kDa. All have binding sites for NADPH, FAD, and FMN near the carboxyl terminus (the reductase domain), and binding sites for tetrahydrobiopterin (BH₄) and heme near the amino terminus (the oxygenase domain). The reductase and oxygenase domains are linked by a calmodulin (CaM) binding site. Occupation of this site facilitates electron transfer from the cofactors in the reductase domain to heme during nitric oxide production. NOS catalyzes the conversion of arginine to citrulline and nitric oxide (NO). Neuronal nitric oxide synthase (nNOS, bNOS, cNOS, Type I) is associated with the post-synaptic density protein (PSD-95) in the neuronal membrane. In response to increased intracellular Ca²⁺, nNOS interacts with CaM. The Ca²⁺-CaM complex, in combination with BH₄, binds to nNOS and induces its translocation from the plasma membrane to the cytoplasm. The dephosphorylation of nNOS by calcineurin initiates the production NO. NO activates guanylyl cyclase (GC) and activates the various cGMP-regulated signaling pathways. nNOS is in activated by phosphorylation by protein kinase A (PKA) or protein kinase C (PKC).

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References:

Dawson, T.M., et al., Regulation of neuronal nitric oxide synthase and identification of novel nitric oxide signaling pathways. Prog. Brain Res., 118, 3-11 (1998).

Wang, Y., et al., Nitric oxide synthases: gene structure and regulation. Adv. Pharmacol., 34, 71-90 (1995).