期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：51
DOI：10.1073/pnas.2110641118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
The taste of acids is critical for animal survival since it enables them to differentiate potentially dangerous from nutritious foods. Due to the general requirement for acid taste for survival, we tested the idea that the receptor mechanism functioning in acid taste may be evolutionarily conserved. Here, we demonstrate that mutation of a
Drosophila gene,
Otopetrin-Like A (
OtopLA), encoding a protein distantly related to the recently identified mammalian acid taste receptor, OTOP1, is essential for both the strong repulsion to highly acidic food and mild attraction to low acidity. The mild attraction and strong aversion to acids requires expression of
OtopLA in distinct taste neurons in the fly equivalent of the vertebrate tongue.
Receptors for bitter, sugar, and other tastes have been identified in the fruit fly
Drosophila melanogaster, while a broadly tuned receptor for the taste of acid has been elusive. Previous work showed that such a receptor was unlikely to be encoded by a gene within one of the two major families of taste receptors in
Drosophila, the “gustatory receptors” and “ionotropic receptors.” Here, to identify the acid taste receptor, we tested the contributions of genes encoding proteins distantly related to the mammalian Otopertrin1 (OTOP1) proton channel that functions as a sour receptor in mice. RNA interference (RNAi) knockdown or mutation by CRISPR/Cas9 of one of the genes,
Otopetrin-Like A (
OtopLA), but not of the others (
OtopLB or
OtopLC) severely impaired the behavioral rejection to a sweet solution laced with high levels of HCl or carboxylic acids and greatly reduced acid-induced action potentials measured from taste hairs. An isoform of
OtopLA that we isolated from the proboscis was sufficient to restore behavioral sensitivity and acid-induced action potential firing in
OtopLA mutant flies. At lower concentrations, HCl was attractive to the flies, and this attraction was abolished in the
OtopLA mutant. Cell type–specific rescue experiments showed that
OtopLA functions in distinct subsets of gustatory receptor neurons for repulsion and attraction to high and low levels of protons, respectively. This work highlights a functional conservation of a sensory receptor in flies and mammals and shows that the same receptor can function in both appetitive and repulsive behaviors.
