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Norway

PMID:26302205  

The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing.

Qing Fang | Artur A Indzhykulian | Mirna Mustapha | Gavin P Riordan | David F Dolan | Thomas B Friedman | Inna A Belyantseva | Gregory I Frolenkov | Sally A Camper | Jonathan E Bird
eLife | 2015

The precise assembly of inner ear hair cell stereocilia into rows of increasing height is critical for mechanotransduction and the sense of hearing. Yet, how the lengths of actin-based stereocilia are regulated remains poorly understood. Mutations of the molecular motor myosin 15 stunt stereocilia growth and cause deafness. We found that hair cells express two isoforms of myosin 15 that differ by inclusion of an 133-kDa N-terminal domain, and that these isoforms can selectively traffic to different stereocilia rows. Using an isoform-specific knockout mouse, we show that hair cells expressing only the small isoform remarkably develop normal stereocilia bundles. However, a critical subset of stereocilia with active mechanotransducer channels subsequently retracts. The larger isoform with the 133-kDa N-terminal domain traffics to these specialized stereocilia and prevents disassembly of their actin core. Our results show that myosin 15 isoforms can navigate between functionally distinct classes of stereocilia, and are independently required to assemble and then maintain the intricate hair bundle architecture.

Pubmed ID: 26302205

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIDCD NIH HHS, United States
    Id: R01 DC05053
  • Agency: NIDCD NIH HHS, United States
    Id: R01 DC008861
  • Agency: NCI NIH HHS, United States
    Id: P30 CA046592
  • Agency: NCI NIH HHS, United States
    Id: P30 CA46592
  • Agency: NIDCD NIH HHS, United States
    Id: R01 DC005053
  • Agency: Intramural NIH HHS, United States
    Id: Z01 DC000048
  • Agency: NIDCD NIH HHS, United States
    Id: P30 DC005188
  • Agency: NIDCD NIH HHS, United States
    Id: DC000039-18
  • Agency: NIDCD NIH HHS, United States
    Id: T32 DC000039
  • Agency: NIDCD NIH HHS, United States
    Id: DC000048-18
  • Agency: NIDCD NIH HHS, United States
    Id: P30 DC05188
  • Agency: Intramural NIH HHS, United States
    Id: Z01 DC000039

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