Actin at stereocilia tips is regulated by mechanotransduction and ADF/cofilin
| Autor: | Xiayi Liao, Jonathan E. Bird, Nicolas F. Berbari, Inna A. Belyantseva, Melanie Barzik, Benjamin J. Perrin, Lata Balakrishnan, Oisorjo Chakraborty, Jamis McGrath, Pallabi Roy, Christian C. Faaborg-Andersen, Chun-Yu Tung, Bo Zhao, Jinan Li, Thomas B. Friedman |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine macromolecular substances Biology Mechanotransduction Cellular Article General Biochemistry Genetics and Molecular Biology Stereocilia EPS8 Mice 03 medical and health sciences 0302 clinical medicine Hearing otorhinolaryngologic diseases Animals Mechanotransduction Postnatal day Actin Cofilin Actins Cell biology Mice Inbred C57BL 030104 developmental biology Actin Depolymerizing Factors Female sense organs General Agricultural and Biological Sciences 030217 neurology & neurosurgery |
| Zdroj: | Curr Biol |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2020.12.006 |
| Popis: | Stereocilia on auditory sensory cells are actin-based protrusions that mechanotransduce sound into an electrical signal. These stereocilia are arranged into a bundle with three rows of increasing length to form a staircase-like morphology that is required for hearing. Stereocilia in the shorter rows, but not the tallest row, are mechanotransducing because they have force-sensitive channels localized at their tips. The onset of mechanotransduction during mouse postnatal development refines stereocilia length and width. However, it is unclear how actin is differentially regulated between stereocilia in the tallest row of the bundle and the shorter, mechanotransducing rows. Here, we show actin turnover is increased at the tips of mechanotransducing stereocilia during bundle maturation. Correspondingly, from birth to postnatal day 6, these stereocilia had increasing amounts of available actin barbed ends, where monomers can be added or lost readily, as compared with the non-mechanotransducing stereocilia in the tallest row. The increase in available barbed ends depended on both mechanotransduction and MYO15 or EPS8, which are required for the normal specification and elongation of the tallest row of stereocilia. We also found that loss of the F-actin-severing proteins ADF and cofilin-1 decreased barbed end availability at stereocilia tips. These proteins enriched at mechanotransducing stereocilia tips, and their localization was perturbed by the loss of mechanotransduction, MYO15, or EPS8. Finally, stereocilia lengths and widths were dysregulated in Adf and Cfl1 mutants. Together, these data show that actin is remodeled, likely by a severing mechanism, in response to mechanotransduction. |
| Databáze: | OpenAIRE |
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