title: Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking.
abstract: 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.
authors.affiliation: Section of Digestive Diseases, Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Iwakiri
authors.forename: Ayano
authors.initials: A
authors.lastname: Satoh
authors.forename: Suvro
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Derek K
authors.initials: DK
authors.lastname: Toomre
authors.forename: Cecile M
authors.initials: CM
authors.lastname: Chalouni
authors.forename: David
authors.initials: D
authors.lastname: Fulton
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Groszmann
authors.forename: Vijay H
authors.initials: VH
authors.lastname: Shah
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D006056:Golgi Apparatus / Q000378:metabolism; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D026403:S-Nitrosothiols / Q000378:metabolism*
chemical_list: D026403:S-Nitrosothiols; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III