title: Reactive oxygen species-induced actin glutathionylation controls actin dynamics in neutrophils.
abstract: The regulation of actin dynamics is pivotal for cellular processes such as cell adhesion, migration, and phagocytosis and thus is crucial for neutrophils to fulfill their roles in innate immunity. Many factors have been implicated in signal-induced actin polymerization, but the essential nature of the potential negative modulators are still poorly understood. Here we report that NADPH oxidase-dependent physiologically generated reactive oxygen species (ROS) negatively regulate actin polymerization in stimulated neutrophils via driving reversible actin glutathionylation. Disruption of glutaredoxin 1 (Grx1), an enzyme that catalyzes actin deglutathionylation, increased actin glutathionylation, attenuated actin polymerization, and consequently impaired neutrophil polarization, chemotaxis, adhesion, and phagocytosis. Consistently, Grx1-deficient murine neutrophils showed impaired in vivo recruitment to sites of inflammation and reduced bactericidal capability. Together, these results present a physiological role for glutaredoxin and ROS- induced reversible actin glutathionylation in regulation of actin dynamics in neutrophils.
authors.affiliation: Department of Pathology, Harvard Medical School and Department of Lab Medicine, Children's Hospital Boston and Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.
authors.forename: Jiro
authors.initials: J
authors.lastname: Sakai
authors.forename: Jingyu
authors.initials: J
authors.lastname: Li
authors.forename: Kulandayan K
authors.initials: KK
authors.lastname: Subramanian
authors.forename: Subhanjan
authors.initials: S
authors.lastname: Mondal
authors.forename: Besnik
authors.initials: B
authors.lastname: Bajrami
authors.forename: Hidenori
authors.initials: H
authors.lastname: Hattori
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Jia
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Dickinson
authors.forename: Jia
authors.initials: J
authors.lastname: Zhong
authors.forename: Keqiang
authors.initials: K
authors.lastname: Ye
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Chang
authors.forename: Ye-Shih
authors.initials: YS
authors.lastname: Ho
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Hongbo R
authors.initials: HR
authors.lastname: Luo
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000276:immunology; D054477:Glutaredoxins / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding; D011554:Pseudopodia / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000199:Actins; D054477:Glutaredoxins; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases