eLife (Feb 2023)

Chloride ions evoke taste sensations by binding to the extracellular ligand-binding domain of sweet/umami taste receptors

  • Nanako Atsumi,
  • Keiko Yasumatsu,
  • Yuriko Takashina,
  • Chiaki Ito,
  • Norihisa Yasui,
  • Robert F Margolskee,
  • Atsuko Yamashita

DOI
https://doi.org/10.7554/eLife.84291
Journal volume & issue
Vol. 12

Abstract

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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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