White Rose University Consortium logo
University of Leeds logo University of Sheffield logo York University logo

Eps8 regulates hair bundle length and functional maturation of mammalian auditory hair cells

Zampini, V., Ruettiger, L., Johnson, S.L., Franz, C., Furness, D.N., Waldhaus, J., Xiong, H., Hackney, C.M., Holley, M.C., Offenhauser, N., Di Fiore, P.P., Knipper, M., Masetto, S. and Marcotti, W. (2011) Eps8 regulates hair bundle length and functional maturation of mammalian auditory hair cells. PLoS Biology, 9 (4). Art no. e1001048 . ISSN 1544-9173


Download (1064Kb)


Hair cells of the mammalian cochlea are specialized for the dynamic coding of sound stimuli. The transduction of sound waves into electrical signals depends upon mechanosensitive hair bundles that project from the cell's apical surface. Each stereocilium within a hair bundle is composed of uniformly polarized and tightly packed actin filaments. Several stereociliary proteins have been shown to be associated with hair bundle development and function and are known to cause deafness in mice and humans when mutated. The growth of the stereociliar actin core is dynamically regulated at the actin filament barbed ends in the stereociliary tip. We show that Eps8, a protein with actin binding, bundling, and barbed-end capping activities in other systems, is a novel component of the hair bundle. Eps8 is localized predominantly at the tip of the stereocilia and is essential for their normal elongation and function. Moreover, we have found that Eps8 knockout mice are profoundly deaf and that IHCs, but not OHCs, fail to mature into fully functional sensory receptors. We propose that Eps8 directly regulates stereocilia growth in hair cells and also plays a crucial role in the physiological maturation of mammalian cochlear IHCs. Together, our results indicate that Eps8 is critical in coordinating the development and functionality of mammalian auditory hair cells.

Item Type: Article
Copyright, Publisher and Additional Information: © 2011 Zampini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Mechanoelectrical Transducer Channels; Ribbon Synapses; Mechanotransducer Channel; Mouse Cochlea; Guinea-Pig; Myosin VI; Potassium Current; Thyroid-Hormone; CA2+ Dependence; Fast Adaptation
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > School of Biological Sciences (Sheffield) > Department of Biomedical Science (Sheffield)
Depositing User: Miss Anthea Tucker
Date Deposited: 02 Jun 2011 13:38
Last Modified: 14 Jun 2014 06:01
Published Version: http://dx.doi.org/10.1371/journal.pbio.1001048
Status: Published
Publisher: Public Library of Science
Refereed: Yes
Identification Number: 10.1371/journal.pbio.1001048
URI: http://eprints.whiterose.ac.uk/id/eprint/43063

Actions (repository staff only: login required)