Journal article
Nox2 and Rac1 Regulate H2O2-Dependent Recruitment of TRAF6 to Endosomal Interleukin-1 Receptor Complexes
Molecular and cellular biology, Vol.26(1), pp.140-154
01/01/2006
DOI: 10.1128/MCB.26.1.140-154.2006
PMCID: PMC1317618
PMID: 16354686
Abstract
ABSTRACT Reactive oxygen species (ROS) generated by NADPH oxidases (Nox) have been implicated in the regulation of signal transduction. However, the cellular mechanisms that link Nox activation with plasma membrane receptor signaling remain poorly defined. We have found that Nox2-derived ROS influence the formation of an active interleukin-1 (IL-1) receptor complex in the endosomal compartment by directing the H2O2-dependent binding of TRAF6 to the IL-1R1/MyD88 complex. Clearance of both superoxide and H2O2 from within the endosomal compartment significantly abrogated IL-1β-dependent IKK and NF-κB activation. MyD88-dependent endocytosis of IL-1R1 following IL-1β binding was required for the redox-dependent formation of an active endosomal receptor complex competent for IKK and NF-κB activation. Small interfering RNAs to either MyD88 or Rac1 inhibited IL-1β induction of endosomal superoxide and NF-κB activation. However, MyD88 and Rac1 appear to be recruited independently to IL-1R1 following ligand stimulation. In this context, MyD88 binding was required for inducing endocytosis of IL-1R1 following ligand binding, while Rac1 facilitated the recruitment of Nox2 into the endosomal compartment and subsequent redox-dependent recruitment of TRAF6 to the MyD88/IL-1R1 complex. The identification of Nox-active endosomes helps explain how subcellular compartmentalization of redox signals can be used to direct receptor activation from the plasma membrane.
Details
- Title: Subtitle
- Nox2 and Rac1 Regulate H2O2-Dependent Recruitment of TRAF6 to Endosomal Interleukin-1 Receptor Complexes
- Creators
- Qiang Li - Department of Anatomy and Cell BiologyMaged M Harraz - Department of Anatomy and Cell BiologyWeihong Zhou - Department of Anatomy and Cell BiologyLiang N Zhang - Department of Anatomy and Cell BiologyWei Ding - Department of Anatomy and Cell BiologyYulong Zhang - Department of Anatomy and Cell BiologyTim Eggleston - Department of Anatomy and Cell BiologyCharles Yeaman - Department of Anatomy and Cell BiologyBotond Banfi - Department of Anatomy and Cell BiologyJohn F Engelhardt - Department of Anatomy and Cell Biology, Department of Internal Medicine, Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases, College of Medicine, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.26(1), pp.140-154
- DOI
- 10.1128/MCB.26.1.140-154.2006
- PMID
- 16354686
- PMCID
- PMC1317618
- NLM abbreviation
- Mol Cell Biol
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Language
- English
- Date published
- 01/01/2006
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Otolaryngology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984025303302771
Metrics
27 Record Views