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. 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.
Original language | English |
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Pages (from-to) | 701-708 |
Number of pages | 8 |
Journal | Cell Reports |
Volume | 23 |
Issue number | 3 |
DOIs | |
State | Published - Apr 17 2018 |
Bibliographical note
Funding Information:We thank Pietro De Camilli and members of the Gracheva and Bagriantsev laboratories for their contributions throughout the project and Ardem Patapoutian for the gift of mPiezo2 plasmid and HEK293 ΔP1 cells. E.O.A. is an Edward L. Tatum fellow and was supported by the Gruber Foundation . E.R.S. is a postdoctoral fellow of the Arnold and Mabel Beckman Foundation . This study was partly funded by NIH grant 1R01NS091300-01A1 (to E.O.G.) and by NSF CAREER grant 1453167 and NIH NINDS grant 1R01NS097547-01A1 (to S.N.B.).
Funding Information:
We thank Pietro De Camilli and members of the Gracheva and Bagriantsev laboratories for their contributions throughout the project and Ardem Patapoutian for the gift of mPiezo2 plasmid and HEK293ΔP1 cells. E.O.A. is an Edward L. Tatum fellow and was supported by the Gruber Foundation. E.R.S. is a postdoctoral fellow of the Arnold and Mabel Beckman Foundation. This study was partly funded by NIH grant 1R01NS091300-01A1 (to E.O.G.) and by NSF CAREER grant 1453167 and NIH NINDS grant 1R01NS097547-01A1 (to S.N.B.).
Publisher Copyright:
© 2018 The Author(s)
Keywords
- K2P2.1
- Piezo1
- Piezo2
- TMEM150C
- TREK-1
- Tentonin3
- mechano-receptor
- mechano-sensitivity
- mechano-transduction
- trigeminal ganglia
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)