Nematode homologs of the sour taste receptor Otopetrin1 are evolutionarily conserved acid-sensitive proton channels

Shitian Li; Umar Al-Sheikh; Yili Chen; Lijun Kang

doi:10.3389/fcell.2023.1133890

Nematode homologs of the sour taste receptor Otopetrin1 are evolutionarily conserved acid-sensitive proton channels

Front Cell Dev Biol. 2023 Jan 26:11:1133890. doi: 10.3389/fcell.2023.1133890. eCollection 2023.

Authors

Shitian Li^{1

2

3}, Umar Al-Sheikh^{1

2

3}, Yili Chen¹, Lijun Kang^{1

2

3}

Affiliations

¹ Department of Neurobiology and Department of Neurosurgery of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou, China.
³ NHC and CAMS Key Laboratory of Medical Neurobiology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Abstract

Numerous taste receptors and related molecules have been identified in vertebrates and invertebrates. Otopetrin1 has recently been identified as mammalian sour taste receptor which is essential for acid sensation. However, whether other Otopetrin proteins are involved in PH-sensing remains unknown. In C. elegans, there are eight otopetrin homologous genes but their expression patterns and functions have not been reported so far. Through heterologous expression in HEK293T cells, we found that ceOTOP1a can be activated by acid in NMDG⁺ solution without conventional cations, which generated inward currents and can be blocked by zinc ions. Moreover, we found that Otopetrin channels are widely expressed in numerous tissues, especially in sensory neurons in the nematode. These results suggest that the biophysical characteristics of the Otopetrin channels in nematodes are generally conserved. However, a series of single gene mutations of otopetrins, which were constructed by CRISPR-Cas9 method, did not affect either calcium responses in ASH polymodal sensory neurons to acid stimulation or acid avoidance behaviors, suggesting that Otopetrin channels might have diverse functions among species. This study reveals that nematode Otopetrins are evolutionarily conserved acid-sensitive proton channels, and provides a framework for further revealing the function and mechanisms of Otopetrin channels in both invertebrates and vertebrates.

Keywords: Caenorhabditis elegans; acid sensation; calcium imaging; otopetrin channels; sensory receptors.

Grants and funding

This work was supported by the Ministry of Science and Technology of China (STI2030-Major Projects, grant number 2021ZD020330); the National Foundation of Natural Science of China (grant numbers 32271017, 31771113, 31471023); and Zhejiang Provincial Natural Science Foundation (grant number LZ22C090001). We thank the Caenorhabditis Genetic Center (CGC), which is supported by the National Institutes of Health - Office of Research Infrastructure Programs (P40 OD010440), for strains.