Properties, Structures, and Physiological Roles of Three Types of Anion Channels Molecularly Identified in the 2010's

Yasunobu Okada; Ravshan Z Sabirov; Petr G Merzlyak; Tomohiro Numata; Kaori Sato-Numata

doi:10.3389/fphys.2021.805148

Properties, Structures, and Physiological Roles of Three Types of Anion Channels Molecularly Identified in the 2010's

Front Physiol. 2021 Dec 23:12:805148. doi: 10.3389/fphys.2021.805148. eCollection 2021.

Authors

Yasunobu Okada^{1

2

3

4}, Ravshan Z Sabirov⁵, Petr G Merzlyak⁵, Tomohiro Numata⁶, Kaori Sato-Numata^{6

7}

Affiliations

¹ National Institute for Physiological Sciences (NIPS), Okazaki, Japan.
² Department of Physiology, School of Medicine, Aichi Medical University, Nagakute, Japan.
³ Department of Physiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁴ Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan.
⁵ Laboratory of Molecular Physiology, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, Uzbekistan.
⁶ Department of Integrative Physiology, Graduate School of Medicine, Akita University, Akita, Japan.
⁷ Japan Society for the Promotion of Science, Tokyo, Japan.

Abstract

Molecular identification was, at last, successfully accomplished for three types of anion channels that are all implicated in cell volume regulation/dysregulation. LRRC8A plus LRRC8C/D/E, SLCO2A1, and TMEM206 were shown to be the core or pore-forming molecules of the volume-sensitive outwardly rectifying anion channel (VSOR) also called the volume-regulated anion channel (VRAC), the large-conductance maxi-anion channel (Maxi-Cl), and the acid-sensitive outwardly rectifying anion channel (ASOR) also called the proton-activated anion channel (PAC) in 2014, 2017, and 2019, respectively. More recently in 2020 and 2021, we have identified the S100A10-annexin A2 complex and TRPM7 as the regulatory proteins for Maxi-Cl and VSOR/VRAC, respectively. In this review article, we summarize their biophysical and structural properties as well as their physiological roles by comparing with each other on the basis of their molecular insights. We also point out unsolved important issues to be elucidated soon in the future.

Keywords: LRRC8A; SLCO2A1; TMEM206; TRPM7; acidosis; cell swelling; regulatory volume decrease; volume-related anion channels.

Publication types

Review