Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605Biomedical Imaging Group, University of Massachusetts Medical School, Worcester, MA 01605
The canonical T2R signaling pathway. (A) The invariant portion of T2R-mediated signaling in the tongue and extraoral cells/tissues includes bitter compounds binding (outside the cell; not depicted) with the receptors to increase intracellular calcium. (B) The remaining components of the T2R pathway in the taste bud.
The paracrine model of the T2R signaling cascade. (A) In the gut, dietary toxins or bitter compounds from bacteria activate T2Rs in EECs to release the peptide hormone CCK, which acts through CKK2 receptors in the neighboring enterocytes to promote ABCB1 to pump bitter-tasting toxins out of the enterocytes (right). Alternatively, CCK released by EECs can also activate CCK1 receptors on sensory fibers of the vagus nerve to send signals to the brain to limit food intake (left). (B) The paracrine model also operates in mouse SCCs from the nasal organ or VNO and in brush cells from the trachea and bladder, where bitter compounds or N-acyl homoserine lactones, bacterial quorum-sensing molecules, activate bitter-taste signaling to release Ach, which in turn activates sensory fibers to (a) initiate a protective reflex, leading to a decrease in respiratory rate or an increase in bladder contraction; (b) close the VNO duct; or (c) induce neurogenic inflammation in the nasal cavity. (C) In tuft cells from the gut, parasites activate the canonical taste cascade and release IL-25, which in turn increases the number of ILC2s and boosts the secretion of type 2 immune cytokines IL-13 and IL-4; these cytokines subsequently promote the hyperplasia of tuft cells and goblet cells.
The endocrine model of the T2R signaling pathway in EECs. These cells secrete GLP-1, which diffuses across the extracellular fluids to enter the circulation, and in turn stimulate the release of insulin from pancreatic β-cells.