Requirement for an Otopetrin-Like protein for acid taste in <i>Drosophila</i>

Ganguly, Anindya; Chandel, Avinash; Turner, Heather N.; S, Wang; Liman, Emily R.; Montell, Craig

doi:10.1101/2021.06.18.449071

Cited by 3 publications

(5 citation statements)

References 34 publications

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“…Recent studies (including this study) have proposed that sour sensation is quite complex in flies compared with sugar or bitter sensation ( Ganguly et al, 2021 ; Mi et al, 2021 ; Rimal et al, 2019 ; Stanley et al, 2021 ). Wild-type females prefer acid-laced food to lay eggs, which is mediated by the expression of IR25a and IR76b in the GRNs of the tarsal segment ( Chen and Amrein, 2017 ).…”

Section: Discussionmentioning

confidence: 81%

“…Previous studies on IRs and GRs have not been able to conclusively demonstrate their role as molecular sensors for sour taste because none of these studies have demonstrated the direct activation of the IRs by acid. Recently, however, several studies have proposed otopetrin (i.e., a proton-selective channel protein) as a molecular sensor of sour taste in mammals and flies ( Ganguly et al, 2021 ; Mi et al, 2021 ; Tu et al, 2018 ). These studies have demonstrated the direct activation of the otopetrin channel coupled with deficits in acid-mediated behavior, suggesting that this evolutionarily conserved channel protein has a role in proton sensing.…”

Section: Discussionmentioning

confidence: 99%

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Mechanisms of Carboxylic Acid Attraction in Drosophila melanogaster

Shrestha

Lee

2021

Molecules and Cells

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Sour is one of the fundamental taste modalities that enable taste perception in animals. Chemoreceptors embedded in taste organs are pivotal to discriminate between different chemicals to ensure survival. Animals generally prefer slightly acidic food and avoid highly acidic alternatives. We recently proposed that all acids are aversive at high concentrations, a response that is mediated by low pH as well as specific anions in Drosophila melanogaster . Particularly, some carboxylic acids such as glycolic acid, citric acid, and lactic acid are highly attractive to Drosophila compared with acetic acid. The present study determined that attractive carboxylic acids were mediated by broadly expressed Ir25a and Ir76b , as demonstrated by a candidate mutant library screen. The mutant deficits were completely recovered via wild-type cDNA expression in sweet-sensing gustatory receptor neurons. Furthermore, sweet gustatory receptors such as Gr5a , Gr61a , and Gr64a-f modulate attractive responses. These genetic defects were confirmed using binary food choice assays as well as electrophysiology in the labellum. Taken together, our findings demonstrate that at least two different kinds of receptors are required to discriminate attractive carboxylic acids from other acids.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Mechanisms of Carboxylic Acid Attraction in Drosophila melanogaster

Shrestha

Lee

2021

Molecules and Cells

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“…Previous studies have showed that OTOP1 is the sour taste receptor in mice (Zhang et al, 2019) and OtopLA is the sour taste receptor in Drosophila (Ganguly et al, 2021;Mi et al, 2021). The functions of Otopetrins are highly consistent in various species, suggesting that Otopetrin1 may function as the universal sour taste receptor (Frank et al, 2022).…”

Section: Otopetrin Knockout Mutants Do Not Affect Acid Avoidance Beha...mentioning

confidence: 93%

“…Furthermore, Otop1 knockout mice have significantly reduced taste receptor neural responses to both hydrochloric acid and citric acid stimulation (Teng et al, 2019) indicating that OTOP1 is definitely the sour receptor in mice (Zhang et al, 2019). In addition, the Otopetrin-like protein OtopLA is also the sour taste receptor in Drosophila (Ganguly et al, 2021;Mi et al, 2021), suggesting that the Otopetrin1 may function as the universal sour taste receptors across species (Frank et al, 2022). However, it remains unknown whether other Otopetrin channels are required for acid sensation, or they are involved in avoidance behaviors in response to aversive acidic pH.…”

Section: Introductionmentioning

confidence: 99%

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

Al-Sheikh

Chen

et al. 2023

Front. Cell Dev. Biol.

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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.

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“…Most vertebrate genomes encode two related proteins OTOP2 and OTOP3, that also form proton channels (Tu et al 2018) and are expressed in a diverse array of tissues, including in the digestive tract, where mutations in the corresponding genes have been linked to disease (Tu et al 2018;Parikh et al 2019;Qu et al 2019;Yang, Liu, et al 2019). Functional OTOP channels are conserved across species, including in invertebrates where they play roles in acid sensing and biomineralization (Hurle et al 2011;Tu et al 2018;Mi et al 2021;Ganguly et al 2021;Chang et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Structural motifs for subtype-specific pH-sensitive gating of vertebrate otopetrin proton channels

Teng

Kaplan

Liang

et al. 2022

Preprint

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Otopetrin (OTOP) channels are proton-selective ion channels conserved among vertebrates and invertebrates and with no structural similarity to other ion channels. There are three vertebrate OTOP channels (OTOP1, OTOP2, and OTOP3), of which one (OTOP1), functions as a sour taste receptor. Whether OTOP channels are gated by, as well as permeating, protons was not known. Here, by comparing functional properties of the three vertebrate proton channels with patch-clamp recording and cytosolic pH microfluorimetry, we provide evidence that each is gated by external protons. OTOP1 and OTOP3 are both activated by extracellular protons, with a sharp threshold of pHe <6.0 and 5.5 respectively, while OTOP2 is negatively gated by protons, and more conductive at alkaline extracellular pH (>pH 9.0). Strikingly, we found that we could change pH-sensitive gating of OTOP2 and OTOP3 channels by swapping extracellular linkers that connect transmembrane domains. Swaps of linkers within the N domain changed the relative conductance at alkaline pH, while swaps within the C domain tended to change the rates of OTOP3 current activation. We conclude that members of the OTOP channel family are proton-gated (acid-sensitive) proton channels and that the gating apparatus is distributed across multiple extracellular regions within both the N and C domains of the channels. In addition to the taste system, OTOP channels are found in the vestibular and digestive systems, where pH sensitivity may be tuned to specific functions.

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Requirement for an Otopetrin-Like protein for acid taste in Drosophila

Cited by 3 publications

References 34 publications

Mechanisms of Carboxylic Acid Attraction in Drosophila melanogaster

Mechanisms of Carboxylic Acid Attraction in Drosophila melanogaster

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

Structural motifs for subtype-specific pH-sensitive gating of vertebrate otopetrin proton channels

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