TY - JOUR
T1 - Stereocilia-staircase spacing is influenced by myosin III motors and their cargos espin-1 and espin-like
AU - Ebrahim, Seham
AU - Avenarius, Matthew R.
AU - Grati, Mhamed
AU - Krey, Jocelyn F.
AU - Windsor, Alanna M.
AU - Sousa, Aurea D.
AU - Ballesteros, Angela
AU - Cui, Runjia
AU - Millis, Bryan A.
AU - Salles, Felipe T.
AU - Baird, Michelle A.
AU - Davidson, Michael W.
AU - Jones, Sherri M.
AU - Choi, Dongseok
AU - Dong, Lijin
AU - Raval, Manmeet H.
AU - Yengo, Christopher M.
AU - Barr-Gillespie, Peter G.
AU - Kachar, Bechara
N1 - Funding Information:
We thank David Kohrman for genetics advice and Rachel Dumont for assistance with SEM. We received support from the following core facilities: mass spectrometry from the University of Virginia W.M. Keck Biomedical Mass Spectrometry Lab and the OHSU Proteomics Shared Resource (partial support from NIH core grants P30 EY010572 and P30 CA069533; Orbitrap Fusion S10 OD012246); CRISPR-mediated mouse knockouts from OHSU Transgenic Mouse Model Shared Resource; and confocal microscopy from the OHSU Advanced Light Microscopy Core @ The Jungers Center. P.G.B.-G. was supported by NIH grants R01 DC002368, R01 DC011034 and P30 DC005983; C.M.Y. by R01 EY018141, and B.K. by NIH/NIDCD/IRP.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms10833
DO - 10.1038/ncomms10833
M3 - Article
C2 - 26926603
AN - SCOPUS:84959310739
SN - 2041-1723
VL - 7
JO - Nature communications
JF - Nature communications
M1 - 10833
ER -