Myosin-VI Function in Sensory Hair Cells
of the Inner Ear

Myosin-VI is an unconventional myosin with the remarkable property of motility towards the pointed ends of actin filaments, the direction opposite to all other myosins (Wells et al 1999). Shown schematically in Fig 1, myosin-VI is composed of an N-terminal motor domain, a light chain-binding neck region, a 200 amino acid coiled-coil (CC) region and a highly conserved C-terminal globular tail. Of these regions, the neck domain is unusual in that it has a 50 amino acid linker between the end of the motor and the single calmodulin binding 'IQ' motif. It is this linker that likely is responsible for the unique motility of myosin-VI (Wells et al 1999).

Functionally, myosin-VI is essential for the development of the inner ear in the mouse. Myosin-VI mutations are responsible for deafness and balance defects in the Snell's waltzer mouse (Avraham et al 1995). Within the inner ear, a single cell type, the sensory hair cell, expresses myosin-VI. In hair cells, myosin-VI is located throughout the cell body but is highly enriched within an actin-rich structure termed the cuticular plate (Fig. 2) (Avraham et al 1995). The cuticular plate is found at the base of the stereocilia, the actin-based protrusions that serve to sense and transmit mechanoelectrical impulses. As such, the cuticular plate serves to anchor the stereocilia into the apical cytoskeleton of the sensory hair cell. The stereocilia are polarized, with their pointed ends embedded in the cuticular plate, so myosin-VI may also be required to transport components down the stereocilia. Snell's waltzer mice have defects in the assembly of stereocilia and it has been suggested that myosin-VI may be pulling the membranes down between each stereocilium during hair cell development (Self et al 1999).