Regulation of membrane homeostasis by TMC1 mechanoelectrical transduction channels is essential for hearing.

ABSTRACT: The mechanoelectrical transduction (MET) channel in auditory hair cells converts sound into electrical signals, enabling hearing. Transmembrane-like channel 1 and 2 (TMC1 and TMC2) are implicated in forming the pore of the MET channel. Here, we demonstrate that inhibition of MET channels, breakage of the tip links required for MET, or buffering of intracellular Ca^... induces pronounced phosphatidylserine externalization, membrane blebbing, and ectosome release at the hair cell sensory organelle, culminating in the loss of TMC1. Membrane homeostasis triggered by MET channel inhibition requires Tmc1 but not Tmc2, and three deafness-causing mutations in Tmc1 cause constitutive phosphatidylserine externalization that correlates with deafness phenotype. Our resul

SUBMITTER: Ballesteros A 

PROVIDER: S-EPMC9348795 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature