Stereocilia-staircase spacing is influenced by myosin III motors and their cargos espin-1 and espin-like

Seham Ebrahim, Matthew R. Avenarius, Mhamed Grati, Jocelyn F. Krey, Alanna M. Windsor, Aurea D. Sousa, Angela Ballesteros, Runjia Cui, Bryan A. Millis, Felipe T. Salles, Michelle A. Baird, Michael W. Davidson, Sherri M. Jones, Dongseok Choi, Lijin Dong, Manmeet H. Raval, Christopher M. Yengo, Peter G. Barr-Gillespie, Bechara Kachar

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Hair cells tightly control the dimensions of their stereocilia, which are actin-rich protrusions with graded heights that mediate mechanotransduction in the inner ear. Two members of the myosin-III family, MYO3A and MYO3B, are thought to regulate stereocilia length by transporting cargos that control actin polymerization at stereocilia tips. We show that eliminating espin-1 (ESPN-1), an isoform of ESPN and a myosin-III cargo, dramatically alters the slope of the stereocilia staircase in a subset of hair cells. Furthermore, we show that espin-like (ESPNL), primarily present in developing stereocilia, is also a myosin-III cargo and is essential for normal hearing. ESPN-1 and ESPNL each bind MYO3A and MYO3B, but differentially influence how the two motors function. Consequently, functional properties of different motor-cargo combinations differentially affect molecular transport and the length of actin protrusions. This mechanism is used by hair cells to establish the required range of stereocilia lengths within a single cell.

Original languageEnglish (US)
Article number10833
JournalNature communications
Volume7
DOIs
StatePublished - Mar 1 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Ebrahim, S., Avenarius, M. R., Grati, M., Krey, J. F., Windsor, A. M., Sousa, A. D., Ballesteros, A., Cui, R., Millis, B. A., Salles, F. T., Baird, M. A., Davidson, M. W., Jones, S. M., Choi, D., Dong, L., Raval, M. H., Yengo, C. M., Barr-Gillespie, P. G., & Kachar, B. (2016). Stereocilia-staircase spacing is influenced by myosin III motors and their cargos espin-1 and espin-like. Nature communications, 7, [10833]. https://doi.org/10.1038/ncomms10833