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 Ca2+. We demonstrate here that transduction and adaptation require phosphatidylinositol 4,5-bisphosphate (PIP2) for normal kinetics. PIP2 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 PIP2-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 IQ domains of myosin-1c, the motor that mediates slow adaptation, permitting a strong interaction with membranes and likely regulating the motor's activity. PIP2 depletion also causes a loss in transduction current. PIP2 therefore plays an essential role in hair cell adaptation and transduction.