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

Evan O. Anderson; Eve R. Schneider; Jon D. Matson; Elena O. Gracheva; Sviatoslav N. Bagriantsev

doi:10.1016/j.celrep.2018.03.094

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

Evan O. Anderson, Eve R. Schneider, Jon D. Matson, Elena O. Gracheva, Sviatoslav N. Bagriantsev

Biology

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

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
Pages (from-to)	701-708
Number of pages	8
Journal	Cell Reports
Volume	23
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2018.03.094
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)

Access to Document

10.1016/j.celrep.2018.03.094

Cite this

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title = "TMEM150C/Tentonin3 Is a Regulator of Mechano-gated Ion Channels",

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.",

keywords = "K2P2.1, Piezo1, Piezo2, TMEM150C, TREK-1, Tentonin3, mechano-receptor, mechano-sensitivity, mechano-transduction, trigeminal ganglia",

author = "Anderson, {Evan O.} and Schneider, {Eve R.} and Matson, {Jon D.} and Gracheva, {Elena O.} and Bagriantsev, {Sviatoslav N.}",

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: {\textcopyright} 2018 The Author(s)",

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language = "English",

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AU - Schneider, Eve R.

AU - Matson, Jon D.

AU - Gracheva, Elena O.

AU - Bagriantsev, Sviatoslav N.

N1 - 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)

PY - 2018/4/17

Y1 - 2018/4/17

N2 - 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.

AB - 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.

KW - K2P2.1

KW - Piezo1

KW - Piezo2

KW - TMEM150C

KW - TREK-1

KW - Tentonin3

KW - mechano-receptor

KW - mechano-sensitivity

KW - mechano-transduction

KW - trigeminal ganglia

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U2 - 10.1016/j.celrep.2018.03.094

DO - 10.1016/j.celrep.2018.03.094

M3 - Article

C2 - 29669276

AN - SCOPUS:85045001221

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EP - 708

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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