Trafficking and activation of eNOS in epithelial cells.

In mammalian cells, formation of nitric oxide (NO) is catalysed by a family of enzymes termed NO synthases (NOS). There are three isoforms of this enzyme, NOS I, II and III. NOS III was originally cloned and identified in endothelial cells; thus this isoform is commonly called endothelial NOS (eNOS). The physiological role of NO produced by eNOS has been documented in most organs, including the brain, lung, cardiovascular system, kidney, liver, gastrointestinal tract and reproductive organs. The bioavailability of NO in these tissues is determined by the balance between its rate of production and degradation. The rate of NO production by eNOS is ultimately dependent on the activity of the enzyme. In the past years, co- and post-translational modifications such as myristoylation, palmitoylation, phosphorylation, protein-protein interactions and subcellular localization have been shown to play an important role in determining eNOS activity. In order to maintain specificity, the production of most signalling molecules occurs in an organized spatial and temporal pattern. Spatial localization of eNOS has been shown to be regulated by different mechanisms that control its targeting from the Golgi apparatus to the plasma membrane, correct compartmentalization within the membrane, and internalization from the plasma membrane to the cytoplasm after activation. Thus, regulated localization and trafficking of eNOS may be essential in regulating enzyme activity and maintaining the spatial and temporal organization of NO signalling in different cell types.