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

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.