N-Ethylmaleimide-sensitive factor: a redox sensor in exocytosis (original) (raw)

Abstract

Vascular injury triggers endothelial exocytosis of granules, releasing pro-inflammatory and pro-thrombotic mediators into the blood. Nitric oxide (NO) and reactive oxygen species (ROS) limit vascular inflammation and thrombosis by inhibiting endothelial exocytosis. NO decreases exocytosis by regulating the activity of the _N_-ethylmaleimide-sensitive factor (NSF), a central component of the exocytic machinery. NO nitrosylates specific cysteine residues of NSF, thereby inhibiting NSF disassembly of the soluble NSF attachment protein receptor (SNARE). NO also modulates exocytosis of other cells; for example, NO regulates platelet activation by inhibiting α-granule secretion from platelets. Other radicals besides NO can regulate exocytosis as well. For example, H2O2 inhibits exocytosis by oxidizing NSF. Using site-directed mutagenesis, we have defined the critical cysteine residues of NSF, and found that one particular cysteine residue, C264, renders NSF sensitive to oxidative stress. Since radicals such as NO and H2O2 inhibit NSF and decrease exocytosis, NSF may act as a redox sensor, modulating exocytosis in response to changes in oxidative stress.

Corresponding author clowenst@jhmi.edu

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Published Online: 2006-11-02

Published in Print: 2006-10-01