Browsing by Subject "Cellular mechanotransduction"

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    TMIE defines pore and gating properties of the mechanotransduction channel of mammalian cochlear hair cells
    (Cell Press, 2020-07-08) Cunningham, Christopher L.; Qiu, Xufeng; Wu, Zizhen; Zhao, Bo; Peng, Guihong; Kim, Ye-Hyun; Lauer, Amanda; Müller, Ulrich; Otolaryngology -- Head and Neck Surgery, School of Medicine
    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 unitary conductance and ion selectivity. We conclude that TMIE is a subunit of the cochlear mechanotransduction channel and that channel function is regulated by a phospholipid-sensing domain in TMIE with similarity to those in other mechanically gated ion channels.