Identification of TMEM206 proteins as pore of PAORAC/ASOR acid-sensitive chloride channels
- Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Germany
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.
Data availability
Raw data are in part presented in the mansucript (e.g. IHC, Western, clamp traces), and as source data files where data points (such as current densities, ratios of permeability etc) have been extracted from original electrophysiological recordings.
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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.
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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Identification of TMEM206 proteins as pore of PAORAC/ASOR acid-sensitive chloride channels
eLife 8:e49187.
https://doi.org/10.7554/eLife.49187
