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bioRxiv · 10.1101/667600

Identification of TMEM206 proteins as pore of ASOR acid-sensitive chloride channels

Ullrich, F.·Blin, S.·Lazarow, K.·Daubitz, T.·von Kries, J.-P.·Jentsch, T. J.
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Abstract

Acid-sensing ion channels have important functions in physiology and pathology, but the molecular composition of acid-activated anion channels had remained unclear. We now used a genome-wide siRNA screen to molecularly identify the widely expressed acid-sensitive outwardly-rectifying ASOR chloride channel. 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 ASORs 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 ASORs 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.

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Ullrich, F., Blin, S., Lazarow, K., Daubitz, T., von Kries, J.-P., Jentsch, T. J.. 2019-06-11. Identification of TMEM206 proteins as pore of ASOR acid-sensitive chloride channels. https://doi.org/10.1101/667600

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