Identification of TMEM206 proteins as pore of PAORAC/ASOR acid-sensitive chloride channels
- Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Germany
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Abstract
Acid-sensing ion channels have important functions in physiology and pathology, but the molecular composition of acid-activated chloride channels had remained unclear. We now used a genome-wide siRNA screen to molecularly identify the widely expressed acid-sensitive outwardly-rectifying anion channel PAORAC/ASOR. ASOR is formed by TMEM206 proteins which display two transmembrane domains (TMs) and are expressed at the plasma membrane. Ion permeation-changing mutations along the length of TM2 and at the end of TM1 suggest that these segments line ASOR’s pore. While not belonging to a gene family, TMEM206 has orthologs in probably all vertebrates. Currents from evolutionarily distant orthologs share activation by protons, a feature essential for ASOR’s role in acid-induced cell death. TMEM206 defines a novel class of ion channels. Its identification will help to understand its physiological roles and the diverse ways by which anion-selective pores can be formed.
Article and author information
Author details
Funding
H2020 European Research Council (Advanced Grant VOLSIGNAL (#740537))
- Thomas J Jentsch
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Reinhard Jahn, Max Planck Institute for Biophysical Chemistry, Germany
Publication history
- Received: June 10, 2019
- Accepted: July 17, 2019
- Accepted Manuscript published: July 18, 2019 (version 1)
- Version of Record published: July 29, 2019 (version 2)
Copyright
© 2019, Ullrich et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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