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bioRxiv · 10.1101/2022.02.23.481615

Chloride ion evokes taste sensation by binding to the extracellular ligand-binding domain of sweet/umami taste receptors

Atsumi, N.·Yasumatsu, K.·Takashina, Y.·Ito, C.·Yasui, N.·Yamashita, A.
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Abstract

Salt taste sensation is multifaceted: NaCl at low or high concentrations is preferably or aversively perceived through distinct pathways. Cl- is thought to participate in taste sensation through an unknown mechanism. Here we describe Cl- ion binding and the response of taste receptor type 1 (T1r), a receptor family composing sweet/umami receptors. The T1r2a/T1r3 heterodimer from the medaka fish, currently the sole T1r amenable to structural analyses, exhibited a specific Cl- binding in the vicinity of the amino-acid-binding site in the ligand-binding domain (LBD) of T1r3, which is likely conserved across species, including human T1r3. The Cl- binding induced a conformational change in T1r2a/T1r3LBD at sub-to low-mM concentrations similar to canonical taste substances. Furthermore, oral Cl- application to mice increased impulse frequencies of taste nerves connected to T1r-expressing taste cells and promoted their behavioral preferences attenuated by a T1r-specific blocker or T1r3 knock-out. These results suggest that the Cl- evokes taste sensations by binding to T1r, thereby serving as another preferred salt taste pathway at a low concentration.

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Atsumi, N., Yasumatsu, K., Takashina, Y., Ito, C., Yasui, N., Yamashita, A.. 2022-02-24. Chloride ion evokes taste sensation by binding to the extracellular ligand-binding domain of sweet/umami taste receptors. https://doi.org/10.1101/2022.02.23.481615

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