Dynamic modulation of auditory hair cell stereocilia membrane mechanics by the scrambling mechanotransduction complex

Inner ear sensory hair cells convert mechanical deflection of their hair bundle into an electrical signal by gating novel mechanoelectrical transduction (MET) channels. Transmembrane channel-like proteins (TMCs) are a component of the MET machinery and part of a superfamily of molecules whose members are ion channels or lipid scramblases. As the stereocilia membrane modulates MET channels properties and the stereocilia membrane has different properties than the soma, we investigated the potential scramblase activity of the MET machinery using a novel viscosity sensor BODIPY 1c. Developmental, genetic, electrophysiological and pharmacological data demonstrate that both TMC1 and TMC2 are mechanosensitive scramblases as activity depends on MET channel being open. Blockage of scramblase activity unmasks a second process that increases effective membrane viscosity independent of MET machinery. Together our data reveal a dynamic regulation of stereocilia membrane that may underlie the speed and sensitivity of the MET process.