Journal of Cell Science 116, e101-e101 (2003)
Copyright © 2003 The Company of Biologists Limited
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.
Related articles in JCS:
- Nitric oxide signaling specificity — the heart of the problem
- David S. Bredt
JCS 2003 116: 9-15.
[Abstract]
[Full Text]
