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Microbial Metabolite-Stimulated Bitter Taste Receptor T2R14 Signaling Is Modulated by CFTR Interactions

Tejas Gupte1,2, Nisha Singh2, Vikram Bhatia2,3

  • 1Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|May 30, 2026
PubMed

Insights

Mutations in cystic fibrosis transmembrane conductance regulator (CFTR) impact bitter taste receptor (T2R) signaling. This study reveals how CFTR domains interact with T2R14, explaining altered innate immune responses in CFTR-mutant cells.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Immunology

Background:

  • Bitter taste receptors (TAS2Rs or T2Rs) are G protein-coupled receptors (GPCRs) crucial for innate immunity at epithelial surfaces.
  • Cystic fibrosis transmembrane conductance regulator (CFTR) mutations are known to affect T2R-mediated innate immune signaling, but the underlying mechanisms are unclear.

Purpose of the Study:

  • To investigate the biophysical interactions between T2R14 and CFTR.
  • To elucidate how these interactions affect T2R14 signaling pathways.

Main Methods:

  • Utilized multiple biophysical techniques to study T2R14 and CFTR interactions.
  • Analyzed protein-protein binding and downstream signaling outcomes.

Main Results:

  • Identified independent interactions between T2R14 and either the N-terminus or NBD2/C-terminus of CFTR.
  • Demonstrated that agonist-bound T2R14 engages both Gαi and Gαq subunits.
  • Showed that the specific CFTR domain involved dictates signaling bias between Gi and Gq pathways.

Conclusions:

  • The interaction between T2R14, its agonists, and CFTR domains explains altered T2R signaling in CFTR mutant cells.
  • Provides mechanistic insights into the interplay between CFTR function and innate immune responses mediated by bitter taste receptors.
Keywords:
CFTRbiased signalingbitter taste receptormicrobial metabolitesprotein–protein interactions

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