Myosin IIIa boosts elongation of stereocilia by transporting espin 1 to the plus ends of actin filaments

Actin filaments in stereocilia on the surface of inner ear sensory hair cells are continually renewed. Myosin IIIa transports the actin-binding/bundling protein espin to stereocilia tips and cooperates with espin in actin filament elongation. Two proteins implicated in inherited deafness, myosin IIIa 1 , a plus-end-directed motor 2 , and espin 3 , 4 , 5 , 6 , an actin-bundling protein containing the actin-monomer-binding motif WH2, have been shown to influence the length of mechanosensory stereocilia 7 , 8 . Here we report that espin 1, an ankyrin repeat-containing isoform of espin 6 , colocalizes with myosin IIIa at stereocilia tips and interacts with a unique conserved domain of myosin IIIa. We show that combined overexpression of these proteins causes greater elongation of stereocilia, compared with overexpression of either myosin IIIa alone or espin 1 alone. When these two proteins were co-expressed in the fibroblast-like COS-7 cell line they induced a tenfold elongation of filopodia. This extraordinary filopodia elongation results from the transport of espin 1 to the plus ends of F-actin by myosin IIIa and depends on espin 1 WH2 activity. This study provides the basis for understanding the role of myosin IIIa and espin 1 in regulating stereocilia length, and presents a physiological example where myosins can boost elongation of actin protrusions by transporting actin regulatory factors to the plus ends of actin filaments.