Journal article
Inactivation of NADPH oxidase organizer 1 Results in Severe Imbalance
Current biology, Vol.16(2), pp.208-213
2006
DOI: 10.1016/j.cub.2005.12.025
PMID: 16431374
Abstract
Otoconia are biominerals of the vestibular system that are indispensable for the perception of gravity. Despite their importance, the process of otoconia genesis is largely unknown. Reactive oxygen species (ROS) have been recognized for their toxic effects in antimicrobial host defense as well as in aging and carcinogenesis. Enzymes evolved for ROS production belong to the recently discovered NADPH oxidase (Nox) enzyme family
[1]. Here we show that the inactivation of a regulatory subunit, NADPH oxidase organizer 1 (Noxo1), resulted in the severe balance deficit seen in the spontaneous mutant “head slant” (hslt) mice whose phenotype was rescued by Noxo1 transgenes. Wild-type Noxo1 was expressed in the vestibular and cochlear epithelia and was required for ROS production by an oxidase complex. In contrast, the hslt mutation of Noxo1 was biochemically inactive and led to an arrest of otoconia genesis, characterized by a complete lack of calcium carbonate mineralization and an accumulation of otoconial protein, otoconin-90/95 (OC-90/95). These results suggest that ROS generated by a Noxo1-dependent vestibular oxidase are critical for otoconia formation and may be required for interactions among otoconial components. Noxo1 mutants implicate a constructive developmental role for ROS, in contrast to their previously described toxic effects.
Details
- Title: Subtitle
- Inactivation of NADPH oxidase organizer 1 Results in Severe Imbalance
- Creators
- Péter J Kiss - Department of Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Judit Knisz - Department of Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Yuzhou Zhang - Department of Otolaryngology, Head and Neck Surgery, University of Iowa Hospitals and Clinics, University of Iowa, Iowa City, Iowa 52242Jonas Baltrusaitis - Department of Chemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Curt D Sigmund - Transgenic Animal Facility, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Ruediger Thalmann - Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri 63110Richard J.H Smith - Department of Otolaryngology, Head and Neck Surgery, University of Iowa Hospitals and Clinics, University of Iowa, Iowa City, Iowa 52242Elisabeth Verpy - Unité de Génétique des Déficits Sensoriels, INSERM U587, Institut Pasteur, 75724 Paris, Cedex 15, FranceBotond Bánfi - Department of Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Current biology, Vol.16(2), pp.208-213
- DOI
- 10.1016/j.cub.2005.12.025
- PMID
- 16431374
- NLM abbreviation
- Curr Biol
- ISSN
- 0960-9822
- eISSN
- 1879-0445
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2006
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006323302771
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