TMEM150C/Tentonin3 Is a Regulator of Mechano-gated Ion Channels

Summary: Neuronal mechano-sensitivity relies on mechano-gated ion channels, but pathways regulating their activity remain poorly understood. TMEM150C was proposed to mediate mechano-activated current in proprioceptive neurons. Here, we studied functional interaction of TMEM150C with mechano-gated ion channels from different classes (Piezo2, Piezo1, and the potassium channel TREK-1) using two independent methods of mechanical stimulation. We found that TMEM150C significantly prolongs the duration of the mechano-current produced by all three channels, decreases apparent activation threshold in Piezo2, and induces persistent current in Piezo1. We also show that TMEM150C is co-expressed with Piezo2 in trigeminal neurons, expanding its role beyond proprioceptors. Finally, we cloned TMEM150C from the trigeminal neurons of the tactile-foraging domestic duck and showed that it functions similarly to the mouse ortholog, demonstrating evolutionary conservation among vertebrates. Our studies reveal TMEM150C as a general regulator of mechano-gated ion channels from different classes. : Mechano-gated ion channels are essential for somatosensation, proprioception, hearing, vasodilation, and axonal growth. Anderson et al. show that the transmembrane protein TMEM150C facilitates activity of mechano-gated ion channels from different classes: Piezo1/2 and the potassium-selective channel TREK-1. This study reveals a role for TMEM150C as an evolutionarily conserved regulator of mechano-sensitivity. Keywords: TMEM150C, Tentonin3, Piezo1, Piezo2, TREK-1, K2P2.1, mechano-sensitivity, mechano-transduction, mechano-receptor, trigeminal gangli