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

  • Nat Commun. 2016 Mar 1:7:10833. doi: 10.1038/ncomms10833.
Seham Ebrahim  1 ,  Matthew R Avenarius  2 ,  M'hamed Grati  1 ,  Jocelyn F Krey  2 ,  Alanna M Windsor  1 ,  Aurea D Sousa  1 ,  Angela Ballesteros  1 ,  Runjia Cui  1 ,  Bryan A Millis  1 ,  Felipe T Salles  1 ,  Michelle A Baird  3 ,  Michael W Davidson  3 ,  Sherri M Jones  4 ,  Dongseok Choi  5 ,  Lijin Dong  6 ,  Manmeet H Raval  7 ,  Christopher M Yengo  7 ,  Peter G Barr-Gillespie  2 ,  Bechara Kachar  1
Affiliations
  • 1. Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • 2. Oregon Hearing Research Center and Vollum Institute, Oregon Health &Science University, Portland, Oregon 97239, USA.
  • 3. National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, Florida 32310, USA.
  • 4. Department of Special Education and Communication Disorders, University of Nebraska-Lincoln, Lincoln, Nebraska 68583, USA.
  • 5. Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA.
  • 6. Genetic Engineering Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • 7. Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA.
PMID: 26926603 DOI: 10.1038/ncomms10833
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.