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

Cell Rep. 2018 Apr 17;23(3):701-708. doi: 10.1016/j.celrep.2018.03.094.

Abstract

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.

Keywords: K2P2.1; Piezo1; Piezo2; TMEM150C; TREK-1; Tentonin3; mechano-receptor; mechano-sensitivity; mechano-transduction; trigeminal ganglia.

MeSH terms

  • Animals
  • Ducks
  • HEK293 Cells
  • Humans
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Mechanotransduction, Cellular*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / metabolism

Substances

  • Ion Channels
  • Membrane Proteins
  • Potassium Channels, Tandem Pore Domain
  • potassium channel protein TREK-1