Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice

Taylor, Ruth; Bullen, Anwen; Johnson, Stuart L.; Grimm-Günter, Eva Maria; Rivero, Francisco; Marcotti, Walter; Forge, Andrew; Daudet, Nicolas

Abstract

© The Author 2014. Published by Oxford University Press. All rights reserved. Hearing relies on the mechanosensory inner and outer hair cells (OHCs) of the organ of Corti, which convert mechanical deflections of their actin-rich stereociliary bundles into electrochemical signals. Several actin-associated proteins are essential for stereocilia formation and maintenance, and their absence leads to deafness. One of the most abundant actin-bundling proteins of stereocilia is plastin 1, but its function has never been directly assessed. Here, we found that plastin 1 knock-out (Pls1 KO) mice have a moderate and progressive form of hearing loss across all frequencies. Auditory hair cells developed normally in Pls1 KO, but in young adult animals, the stereocilia of inner hair cells were reduced in width and length. The stereocilia of OHCs were comparatively less affected; however, they also showed signs of degeneration in ageing mice. The hair bundle stiffness and the acquisition of the electrophysiological properties of hair cells were unaffected by the absence of plastin 1, except for a significant change in the adaptation properties, but not the size of the mechanoelectrical transducer currents. These results show that in contrast to other actin-bundling proteins such as espin, harmonin or Eps8, plastin 1 is dispensable for the initial formation of stereocilia. However, the progressive hearing loss and morphological defects of hair cells in adult Pls1 KO mice point at a specific role for plastin 1 in the preservation of adult stereocilia and optimal hearing. Hence, mutations in the human PLS1 gene may be associated with relatively mild and progressive forms of hearing loss.

Citation

Taylor, R., Bullen, A., Johnson, S. L., Grimm-Günter, E. M., Rivero, F., Marcotti, W., Forge, A., & Daudet, N. (2015). Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice. Human molecular genetics, 24(1), 37-49. https://doi.org/10.1093/hmg/ddu417

• Journal Article Type: Article
• Acceptance Date: Aug 10, 2014
• Online Publication Date: Aug 14, 2014
• Publication Date: Jan 1, 2015
• Deposit Date: Sep 21, 2021
• Publicly Available Date: Sep 29, 2021
• Journal: Human Molecular Genetics
• Print ISSN: 0964-6906
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Issue: 1
• Pages: 37-49
• DOI: https://doi.org/10.1093/hmg/ddu417
• Keywords: Actins; Adult; Auditory hair cell; Inner auditory hair cells; Transducers; Mice; Hearing loss; Stereocilium
• Public URL: https://hull-repository.worktribe.com/output/540837