8.A.113. The Tentonin or TMEM150 (TMEM150) Family
Touch sensation or proprioception requires the transduction of mechanical stimuli into electrical signals by mechanoreceptors. These mechanoreceptors involve transducer channels. Although Piezo1 and 2 are mechanically activated (MA) channels with rapid inactivation, MA molecules with slow inactivation kinetics exist. TMEM150c has been reported to either be a channel protein or a Piezo channel protein modifiier. Hong et al. 2016 reported that heterologously expressed Tentonin3 (TTN3)/TMEM150C is activated by mechanical stimuli with slow inactivation kinetics. Genetic ablation of Ttn3/Tmem150c markedly reduced slowly adapting neurons in dorsal-root ganglion neurons. The MA TTN3 currents were inhibited by known blockers of mechanosensitive ion channels, and TTN3 was localized in muscle spindle afferents. Ttn3-deficient mice exhibited the loss of coordinated movements and abnormal gait. Thus, TTN3 appears to be a component of a mechanosensitive channel with a slow inactivation rate and contributes to motor coordination (Hong et al. 2016). Dubin et al. 2017 showed that if Piezo1 was deleted in mice, no such current was observed. However, Hong et al. 2017 concluded that TTN3 is a channel protein, but Anderson et al. 2018 reported functional interaction of TMEM150C with mechano-gated ion channels from different classes (Piezo2, Piezo1, and the potassium channel TREK-1). TMEM150C significantly prolongs the duration of the mechano-current produced by all three channels, decreases the apparent activation threshold in Piezo2, and induces persistent current in Piezo1. They also showed that TMEM150C is co-expressed with Piezo2 in trigeminal neurons, expanding its role beyond proprioceptors (Anderson et al. 2018). It should be noted that this controversy in not yet resolved. For example, Ojeda-Alonso et al. 2022 could not demonstrate channel activity for TMEM150.