Vertebrate OTOP1 is also an alkali-activated channel

Lifeng Tian, Hao Zhang, Shilong Yang, Anna Luo, Peter Muiruri Kamau, Jingmei Hu, Lei Luo () and Ren Lai ()
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Lifeng Tian: Chinese Academy of Sciences
Hao Zhang: Chinese Academy of Sciences
Shilong Yang: Northeast Forestry University
Anna Luo: Chinese Academy of Sciences
Peter Muiruri Kamau: Chinese Academy of Sciences
Jingmei Hu: Chinese Academy of Sciences
Lei Luo: Chinese Academy of Sciences
Ren Lai: Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: Abstract Although alkaline sensation is critical for survival, alkali-activated receptors are yet to be identified in vertebrates. Here, we showed that the OTOP1 channel can be directly activated by extracellular alkali. Notably, OTOP1 biphasically mediated proton influx and efflux with extracellular acid and base stimulation, respectively. Mutations of K221 and R554 at the S5–S6 and S11–S12 linkers significantly reduced alkali affinity without affecting acid activation, suggesting that different domains are responsible for acid- and alkali-activation of OTOP1. The selectivity for H+ was significantly higher in OTOP1 activated by alkali than that by acid, further suggesting that the two activations might be independent gating processes. Given that the alkali-activation of OTOP1 and the required key residues were conserved in the six representative vertebrates, we cautiously propose that OTOP1 participates in alkaline sensation in vertebrates. Thus, our study identified OTOP1 as an alkali-activated channel.

Date: 2023
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DOI: 10.1038/s41467-022-35754-9

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