title: Stereocilia-staircase spacing is influenced by myosin III motors and their cargos espin-1 and espin-like.
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.
authors.affiliation: Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Seham
authors.initials: S
authors.lastname: Ebrahim
authors.affiliation: Oregon Hearing Research Center and Vollum Institute, Oregon Health &Science University, Portland, Oregon 97239, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Avenarius
authors.affiliation: Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: M'hamed
authors.initials: M
authors.lastname: Grati
authors.affiliation: Oregon Hearing Research Center and Vollum Institute, Oregon Health &Science University, Portland, Oregon 97239, USA.
authors.forename: Jocelyn F
authors.initials: JF
authors.lastname: Krey
authors.affiliation: Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Alanna M
authors.initials: AM
authors.lastname: Windsor
authors.affiliation: Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Aurea D
authors.identifier: http://orcid.org/0000-0002-9153-7414
authors.initials: AD
authors.lastname: Sousa
authors.affiliation: Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Ballesteros
authors.affiliation: Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Runjia
authors.initials: R
authors.lastname: Cui
authors.affiliation: Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Millis
authors.affiliation: Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Felipe T
authors.initials: FT
authors.lastname: Salles
authors.affiliation: National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, Florida 32310, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Baird
authors.affiliation: National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, Florida 32310, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Davidson
authors.affiliation: Department of Special Education and Communication Disorders, University of Nebraska-Lincoln, Lincoln, Nebraska 68583, USA.
authors.forename: Sherri M
authors.initials: SM
authors.lastname: Jones
authors.affiliation: Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Dongseok
authors.initials: D
authors.lastname: Choi
authors.affiliation: Genetic Engineering Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Lijin
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA.
authors.forename: Manmeet H
authors.initials: MH
authors.lastname: Raval
authors.affiliation: Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Yengo
authors.affiliation: Oregon Hearing Research Center and Vollum Institute, Oregon Health &Science University, Portland, Oregon 97239, USA.
authors.forename: Peter G
authors.identifier: http://orcid.org/0000-0002-9787-5860
authors.initials: PG
authors.lastname: Barr-Gillespie
authors.affiliation: Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Bechara
authors.initials: B
authors.lastname: Kachar
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D007758:Ear, Inner / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D025102:Myosin Type III / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D059547:Stereocilia / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: C558785:MYO3A protein, mouse; C572903:MYO3B protein, mouse; D008840:Microfilament Proteins; C104108:espin protein, mouse; D025102:Myosin Type III; D018995:Myosin Heavy Chains