Hair cells require phosphatidylinositol 4,5-bisphosphate for mechanical transduction and adaptation

After opening in response to mechanical stimuli, hair cell transduction channels adapt with fast and slow mechanisms that each depend on Call. We demonstrate here that transduction and adaptation require phosphatidylinositol 4,5-bisphosphate (PIP2) for normal kinetics. PlP(2) has a striking distribution in hair cells, being excluded from the basal region of hair bundles and apical surfaces of frog saccular hair cells. Localization of a phosphatidylinositol lipid phosphatase, Ptprq, to these PlP(2)-free domains suggests that Ptprq maintains low PIP2 levels there. Depletion of PIP2 by inhibition of phosphatidylinositol 4-kinase or sequestration by aminoglycosides reduces the rates of fast and slow adaptation. PIP2 and other anionic phospholipids bind directly to the 10 domains of myosin-1c, the motor that mediates slow adaptation, permitting a strong interaction with membranes and likely regulating the motor's activity. PlP2 depletion also causes a loss in transduction current. PlP2 therefore plays an essential role in hair cell adaptation and transduction.