Mechanoelectrical Transduction Without Myosin XVa

Sensory cells of the inner ear, the hair cells detect sound, gravity, and acceleration forces through deflection of stereocilia that are arranged in rows of precisely graded heights. A loss of function mutation in any of the proteins responsible for formation of the stereocilia bundle usually results in the disruption of the bundle and loss of mechanosensitivity. Only in few exceptional cases it was possible to study role of a particular protein in mechanosensitivity separately from its role in maintenance of hair bundle structure. Our preliminary data show that in auditory hair cells of shaker 2 mouse the mechanosensing machinery is mostly intact, in spite of the fact that stereocilia of these cells do not grow normally due to absence of functional myosin XVa. The proposed study will determine major features of mechanotransduction current in these cells: 1) directional sensitivity; 2) maximal size and sensitivity to bundle deflection; 3) percentage of the open mechanosensitive channels at rest; 4) the extent of adaptation responses; 5) changes during stereocilia degeneration. The expected results will establish the role of myosin XVa based stereocilia elongation complex in mechanotransduction and will start answering the question of how exactly the precise organization of stereocilia shapes mechanotransduction.