Myosin VIIa is a newly identified member of the
myosin superfamily of actin-based motors. Recently, the
myosin VIIa gene was identified as the gene defective in shaker-1, a recessive
deafness in mice [Gibson, F., Walsh, J., Mburu, P., Varela, A., Brown, K.A., Antonio, M., Beisel, K.W., Steel, K.P. & Brown, S.D.M. (1995) Nature (London) 374, 62-64], and in human
Usher syndrome type 1B, an inherited disease characterized by congenital
deafness, vestibular dysfunction, and
retinitis pigmentosa [Weil, D., Blanchard, S., Kaplan, J., Guilford, P., Gibson, F., Walsh, J., Mburu, P., Varela, A., Levilliers, J., Weston, M.D., Kelley, P.M., Kimberling, W.J., Wagenaar, M., Levi-Acobas, F., Larget-Piet, D., Munnich, A., Steel, K.P., Brown, S.D.M. & Petit, C. (1995) Nature (London) 374, 60-61]. To understand the normal function of
myosin VIIa and how it could cause these disease phenotypes when defective, we generated
antibodies specific to the tail portion of this unconventional
myosin. We found that
myosin VIIa was expressed in cochlea, retina, testis, lung, and kidney. In cochlea,
myosin VIIa expression was restricted to the inner and outer hair cells, where it was found in the apical stereocilia as well as the cytoplasm. In the eye,
myosin VIIa was expressed by the
retinal pigmented epithelial cells, where it was enriched within the apical actin-rich domain of this cell type. The cell-specific localization of
myosin VIIa suggests that the
blindness and
deafness associated with
Usher syndrome is due to lack of proper
myosin VIIa function within the cochlear hair cells and the
retinal pigmented epithelial cells.