Reactive Oxygen Species-Induced Actin Glutathionylation Controls Actin Dynamics in Neutrophils

• Type of Material: Article
• Authors: Jiro Sakai, Harvard University; Jingyu Li, Harvard University; Kulandayan K. Subramanian, Harvard University; Subhanjan Mondal, Harvard University; Besnik Bajrami, Harvard University; Hidenori Hattori, Harvard University; Yonghui Jia, Harvard University; Bryan C. Dickinson, University of California, Berkeley; Jia Zhong, Harvard University; Keqiang Ye, Emory University; Christopher J. Chang, University of California, Berkeley; Ye-Shih Ho, Wayne State University; Jun Zhou, Emory University; Hongbo R. Luo, Harvard University
• Language: English
• Date: 2012-12-14
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.immuni.2012.08.017
• Title of Journal or Parent Work: Immunity
• ISSN: 1074-7613
• Volume: 37
• Issue: 6
• Start Page: 1037
• End Page: 1049
• Grant/Funding Information: C.J. Chang is supported by NIH GM 79465 and is an investigator with the Howard Hughes Medical Institute.; H. Luo is supported by NIH grants HL085100 and GM076084.
• Keywords: MICE; GLUTAREDOXIN; REDOX; Life Sciences & Biomedicine; S-GLUTATHIONYLATION; BETA-ACTIN; Immunology; Science & Technology; LUNG INFLAMMATION; SIGNAL-TRANSDUCTION
• Research Categories: Chemistry, Biochemistry; Health Sciences, Pathology; Health Sciences, Immunology

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.