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

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2012 Nov 20

PMID 23159440

Citations 103

Authors

Jiro Sakai

Jingyu Li

Kulandayan K Subramanian

Subhanjan Mondal

Besnik Bajrami

Hidenori Hattori

Yonghui Jia

Bryan C Dickinson

Jia Zhong

Keqiang Ye

Christopher J Chang

Ye-Shih Ho

Jun Zhou

Hongbo R Luo

Affiliations

Soon will be listed here.

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.

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