Yasuko Iwakiri1,2,3,4,5, Ayano Satoh6,5, Suvro Chatterjee7, Derek Toomre6,8, Cécile Chalouni6,5, David Fulton9, Roberto J. Groszmann1,2,4,5, Vijay H. Shah7, William C. Sessa3,5
1*Section of Digestive Diseases,
2Department of Veterans Affairs
3Departments of Pharmacology and
4Hepatic Hemodynamic Laboratory, VA Connecticut Healthcare System, West Haven, CT 06516;
5Yale University
6Cell Biology, and
7Gastroenterology Research Unit, Department of Physiology and Tumor Biology Program, Mayo Clinic, Rochester, MN 55905; and
8Institute for Cancer Research, Yale University School of Medicine, New Haven, CT 06510;
9**Vascular Biology Center and Department of Pharmacology, Medical College of Georgia, Augusta, GA 30912
Tóm tắt
Nitric oxide (NO) is a highly diffusible and short-lived physiological messenger. Despite its diffusible nature, NO modifies thiol groups of specific cysteine residues in target proteins and alters protein function via S-nitrosylation. Although intracellular S-nitrosylation is a specific posttranslational modification, the defined localization of an NO source (nitric oxide synthase, NOS) with protein S-nitrosylation has never been directly demonstrated. Endothelial NOS (eNOS) is localized mainly on the Golgi apparatus and in plasma membrane caveolae. Here, we show by using eNOS targeted to either the Golgi or the nucleus that S-nitrosylation is concentrated at the primary site of eNOS localization. Furthermore, localization of eNOS on the Golgi enhances overall Golgi protein S-nitrosylation, the specific S-nitrosylation of
N
-ethylmaleimide-sensitive factor and reduces the speed of protein transport from the endoplasmic reticulum to the plasma membrane in a reversible manner. These data indicate that local NOS action generates organelle-specific protein S-nitrosylation reactions that can regulate intracellular transport processes.
