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Loss of Baiap2l2 destabilizes the transducing stereocilia of cochlear hair cells and leads to deafness

Carlton, AJ; Halford, J; Underhill, A; Jeng, J-Y; Avenarius, MR; Gilbert, ML; Ceriani, F; ... Marcotti, W; + view all (2021) Loss of Baiap2l2 destabilizes the transducing stereocilia of cochlear hair cells and leads to deafness. The Journal of Physiology , 599 (4) pp. 1173-1198. 10.1113/JP280670. Green open access

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Abstract

The transduction of sound waves into electrical signals depends upon mechanosensitive stereociliary bundles that project from the apical surface of hair cells within the cochlea. The height and width of these actin‐based stereocilia is tightly regulated throughout life to establish and maintain their characteristic staircase‐like structure, which is essential for normal mechanoelectrical transduction. Here, we show that BAIAP2L2, a member of the I‐BAR protein family, is a newly identified hair bundle protein that is localized to the tips of the shorter rows of transducing stereocilia in mouse cochlear hair cells. BAIAP2L2 was detected by immunohistochemistry from postnatal day 2.5 (P2.5) throughout adulthood. In Baiap2l2 deficient mice, outer hair cells (OHCs), but not inner hair cells (IHCs), began to lose their third row of stereocilia and showed a reduction in the size of the mechanoelectrical transducer current from just after P9. Over the following post‐hearing weeks, the ordered staircase structure of the bundle progressively deteriorates, such that, by 8 months of age, both OHCs and IHCs of Baiap2l2 deficient mice have lost most of the second and third rows of stereocilia and become deaf. We also found that BAIAP2L2 interacts with other key stereociliary proteins involved in normal hair bundle morphogenesis, such as CDC42, RAC1, EPS8 and ESPNL. Furthermore, we show that BAIAP2L2 localization to the stereocilia tips depends on the motor protein MYO15A and its cargo EPS8. We propose that BAIAP2L2 is key to maintenance of the normal actin structure of the transducing stereocilia in mature mouse cochlear hair cells.

Type: Article
Title: Loss of Baiap2l2 destabilizes the transducing stereocilia of cochlear hair cells and leads to deafness
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1113/JP280670
Publisher version: https://doi.org/10.1113/JP280670
Language: English
Additional information: Copyright © 2020 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: actin, cochlear, development, hearing loss, mechanoelectrical transduction, mouse, stereocilia
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10115147
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