TMIE Defines Pore and Gating Properties of the Mechanotransduction Channel of Mammalian Cochlear Hair Cells.

ABSTRACT: TMC1 and TMC2 (TMC1/2) have been proposed to form the pore of the mechanotransduction channel of cochlear hair cells. Here, we show that TMC1/2 cannot form mechanotransduction channels in cochlear hair cells without TMIE. TMIE binds to TMC1/2, and a TMIE mutation that perturbs TMC1/2 binding abolishes mechanotransduction. N-terminal TMIE deletions affect the response of the mechanotransduction channel to mechanical force. Similar to mechanically gated TREK channels, the C-terminal cytoplasmic TMIE domain contains charged amino acids that mediate binding to phospholipids, including PIP₂. TMIE point mutations in the C terminus that are linked to deafness disrupt phospholipid binding, sensitize the channel to PIP₂ depletion from hair cells, and alter the channel's unitar

SUBMITTER: Cunningham CL 

PROVIDER: S-EPMC7351599 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature