PIEZO2 channels mediate rapidly adapting mechanically activated currents in peripheral sensory neurons of the dorsal root ganglia (DRG), and they are indispensable for light touch and proprioception. Relatively little is known about what other proteins regulate PIEZO2 activity in a cellular context. TMEM120A (TACAN) was proposed to act as a high threshold mechanically activated ion channel in nociceptive DRG neurons. Here, we find that Tmem120a coexpression decreased the amplitudes of mechanically activated PIEZO2 currents and increased their threshold of activation. TMEM120A did not inhibit mechanically activated PIEZO1 and TREK1 channels and TMEM120A alone did not result in the appearance of mechanically activated currents above background. Tmem120a and Piezo2 expression in mouse DRG neurons overlapped, and siRNA-mediated knockdown of Tmem120a increased the amplitudes of rapidly adapting mechanically activated currents and decreased their thresholds to mechanical activation. Our data identify TMEM120A as a negative modulator of PIEZO2 channel activity, and do not support TMEM120A being a mechanically activated ion channel.
Skip Nav Destination
Article navigation
1 August 2022
Communication|
Mechanotransduction by Membrane Proteins|
July 12 2022
TMEM120A/TACAN inhibits mechanically activated PIEZO2 channels
John Smith Del Rosario
,
John Smith Del Rosario
*
1
Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ
Search for other works by this author on:
Matthew Gabrielle
,
Matthew Gabrielle
*
1
Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ
Search for other works by this author on:
Yevgen Yudin
,
Yevgen Yudin
1
Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ
Search for other works by this author on:
Tibor Rohacs
1
Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ
Correspondence to Tibor Rohacs: tibor.rohacs@rutgers.edu
Search for other works by this author on:
John Smith Del Rosario
*
1
Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ
Matthew Gabrielle
*
1
Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ
Yevgen Yudin
1
Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ
Correspondence to Tibor Rohacs: tibor.rohacs@rutgers.edu
*
J.S. Del Rosario and M. Gabrielle contributed equally to this paper.
J.S. Del Rosario’s present address is Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO.
This work is part of a special issue on mechanotransduction by membrane proteins.
Received:
March 28 2022
Accepted:
June 24 2022
Online Issn: 1540-7748
Print Issn: 0022-1295
Funding
Funder(s):
National Institutes of Health
- Award Id(s): R01-NS055159,F31-NS100484,F99-NS113422
© 2022 Del Rosario et al.
2022
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Gen Physiol (2022) 154 (8): e202213164.
Article history
Received:
March 28 2022
Accepted:
June 24 2022
Citation
John Smith Del Rosario, Matthew Gabrielle, Yevgen Yudin, Tibor Rohacs; TMEM120A/TACAN inhibits mechanically activated PIEZO2 channels. J Gen Physiol 1 August 2022; 154 (8): e202213164. doi: https://doi.org/10.1085/jgp.202213164
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Sign in via your Institution
Sign in via your Institution
303
Views
0
Citations
Suggested Content
Characterizing the lipid fingerprint of the mechanosensitive channel Piezo2
J Gen Physiol (July,2022)
C. elegans PEZO-1 is a mechanosensitive ion channel involved in food sensation
J Gen Physiol (December,2021)
Piezo1–Pannexin1 complex couples force detection to ATP secretion in cholangiocytes
J Gen Physiol (October,2021)
Advertisement