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Nitric oxide signalling compartments

Unlike most other chemical mediators, NO cannot be stored or synthesized in an inactive form, since it is a gaseous free radical. Its synthesis must therefore be carefully controlled. Indeed NO synthases (NOSs) have proven to be very tightly regulated — primarily by increases in local Ca²⁺ levels. In a Commentary on p. 9, David Bredt discusses recent work indicating that NOS regulation extends to its subcellular compartmentalization. Studies of skeletal muscle have revealed that the nNOSµ isoform interacts with the dystrophin-associated protein syntrophin through its PDZ domain. This localizes it to the sarcolemma, allowing efficient coupling of Ca²⁺ influx to generation of NO, which promotes vasodilation and therefore increased supply of blood to the muscle. In neurons, the nNOS PDZ domain has a similar role: it targets the enzyme to NMDA receptors in the post-synaptic density, allowing specific activation of synaptic ion channels and guanylyl cyclase. Subcellular targeting of the eNOS isoform, by contrast, depends on its myristoylation/palmitoylation, which targets the enzyme to caveolae and consequently various signalling molecules. The importance of such targeting mechanisms is particularly evident in the heart, where nNOS and eNOS have opposing effects on contractility.

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Related articles in JCS:

Nitric oxide signaling specificity — the heart of the problem

David S. Bredt
JCS 2003 116: 9-15. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?