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.
Highlights
Hair cells tightly control the dimensions of their stereocilia, which are actin-rich protrusions with graded heights that mediate mechanotransduction in the inner ear
Using immunofluorescence in utricular wholemounts, we found that the myosin-III paralogs and their espin-related cargos showed striking enrichment in either striola (ESPNL and MYO3A) or extrastriola (ESPN-1 and MYO3B) zones (Fig. 2i–m)
We show here that MYO3A and MYO3B, along with their actinregulating cargos ESPN-1 and ESPNL, form a cooperative system whereby different motor-cargo combinations control the number and length of actin protrusions produced by a cell
Summary
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. 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. We identified a novel myosin-III cargo, espin-like (ESPNL), which appears early in bundle development and is essential for normal auditory function. We show that these two myosins and their two cargos form a system that influences the number and the length of actin protrusions, and is critical for the formation of the normal stereocilia-staircase structure
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