Ankyrin Is An Intracellular Tether for TMC Mechanotransduction Channels

Mechanotransduction channels have been proposed as force sensors in various physiological processes, such as hearing and touch. In particular, TMC1 has been shown to constitute the pore of hair cell mechanotransduction channels, but little is known about how force is sensed by TMC channels. Here, we identify UNC-44/ankyrin as an essential component of the TMC-1 mechanotransduction channel complex in the sensory cilia of Caenorhabditis elegans mechanoreceptor neurons. Ankyrin binds indirectly to TMC-1 via evolutionarily conserved CIB proteins, which are required for TMC-1-mediated mechanosensation in C. elegans OLQ neurons and body wall muscles. Mechanosensory activity conferred by ectopically expressed TMCs in mechanoinsensitive neurons depends on both ankyrin and CIB proteins, indicating that the ankyrin-CIB subcomplex is required for TMC mechanosensitivity. Our work indicates that ankyrin is a long-sought intracellular tether that transmits force to TMC mechanotransduction channels. [Display omitted] •TMC-1 functions as a mechanosensor in C. elegans neurons and muscles•UNC-44/ankyrin binds indirectly to TMC-1 via CALM-1•CALM-1 and ankyrin are required for TMC-1-mediated mechanosensation•Ankyrin acts as an intracellular tether to confer mechanosensitivity to TMC channels TMC channels are important for sensory transduction, notably as key components of the hair cell mechanotransducer. In this issue of Neuron, Tang et al. show that the mechanosensory activity of C. elegans TMCs requires the intracellular tether ankyrin, which interacts with TMC-1 through the adaptor protein CALM-1.