TY - JOUR
T1 - Subcellular targeting and trafficking of nitric oxide synthases
AU - Oess, Stefanie
AU - Icking, Ann
AU - Fulton, David
AU - Govers, Roland
AU - Müller-Esterl, Werner
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/6/15
Y1 - 2006/6/15
N2 - Unlike most other endogenous messengers that are deposited in vesicles, processed on demand and/or secreted in a regulated fashion, NO (nitric oxide) is a highly active molecule that readily diffuses through cell membranes and thus cannot be stored inside the producing cell. Rather, its signalling capacity must be controlled at the levels of biosynthesis and local availability. The importance of temporal and spatial control of NO production is highlighted by the finding that differential localization of NO synthases in cardiomyocytes translates into distinct effects of NO in the heart. Thus NO synthases belong to the most tightly controlled enzymes, being regulated at transcriptional and translational levels, through co- and post-translational modifications, by substrate availability and not least via specific sorting to subcellular compartments, where they are in close proximity to their target proteins. Considerable efforts have been made to elucidate the molecular mechanisms that underlie the intracellular targeting and trafficking of NO synthases, to ultimately understand the cellular pathways controlling the formation and function of this powerful signalling molecule. In the present review, we discuss the mechanisms and triggers for subcellular routing and dynamic redistribution of NO synthases and the ensuing consequences for NO production and action.
AB - Unlike most other endogenous messengers that are deposited in vesicles, processed on demand and/or secreted in a regulated fashion, NO (nitric oxide) is a highly active molecule that readily diffuses through cell membranes and thus cannot be stored inside the producing cell. Rather, its signalling capacity must be controlled at the levels of biosynthesis and local availability. The importance of temporal and spatial control of NO production is highlighted by the finding that differential localization of NO synthases in cardiomyocytes translates into distinct effects of NO in the heart. Thus NO synthases belong to the most tightly controlled enzymes, being regulated at transcriptional and translational levels, through co- and post-translational modifications, by substrate availability and not least via specific sorting to subcellular compartments, where they are in close proximity to their target proteins. Considerable efforts have been made to elucidate the molecular mechanisms that underlie the intracellular targeting and trafficking of NO synthases, to ultimately understand the cellular pathways controlling the formation and function of this powerful signalling molecule. In the present review, we discuss the mechanisms and triggers for subcellular routing and dynamic redistribution of NO synthases and the ensuing consequences for NO production and action.
KW - Acylation cycle
KW - Differential activation
KW - Intracellular trafficking
KW - Nitric oxide synthase
KW - Protein-protein interaction
KW - Subcellular targeting
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U2 - 10.1042/BJ20060321
DO - 10.1042/BJ20060321
M3 - Review article
C2 - 16722822
AN - SCOPUS:33744988179
VL - 396
SP - 401
EP - 409
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 3
ER -