T2R14 mediated antimicrobial responses through interactions with CFTR

Abstract

Bitter taste receptors (T2Rs), are a subset of G protein-coupled receptors (GPCRs) that play a key role in responding to microbial presence at epithelial surfaces. In epithelia, the activities of ion channels and transporters, and of T2Rs, mutually affect each other. The normal function of one such anion channel, cystic fibrosis transmembrane conductance regulator (CFTR), is essential for the maintenance of healthy epithelia, not just in the respiratory but in the digestive and reproductive system as well. Based on evidence that T2R14 activity is affected upon mutations in CFTR, we explored the possibility that T2R14 and CFTR directly interact in cell membranes. The biophysical interaction between these proteins was mapped to specific regions of the CFTR, and was dependent on agonist stimulation of T2R14. Further, T2R14 was found to couple to Gαq, in addition to the canonical Gαi, in response to bacterial and fungal quorum sensing molecules. Whether the interaction with CFTR affects T2R14 driven responses to microbial signals is under investigation.