Taste receptor signalling - from tongues to lungs

Abstract

Taste buds are the transducing endorgans of gustation. Each taste bud comprises 50-100 elongated cells, which extend from the basal lamina to the surface of the tongue, where their apical microvilli encounter taste stimuli in the oral cavity. Salts and acids utilize apically located ion channels for transduction, while bitter, sweet and umami (glutamate) stimuli utilize G-protein-coupled receptors (GPCRs) and second-messenger signalling mechanisms. This review will focus on GPCR signalling mechanisms. Two classes of taste GPCRs have been identified, the T1Rs for sweet and umami (glutamate) stimuli and the T2Rs for bitter stimuli. These low affinity GPCRs all couple to the same downstream signalling effectors that include Gβγ activation of phospholipase Cβ2, 1,4,5-inositol trisphosphate mediated release of Ca(2+) from intracellular stores and Ca(2+) -dependent activation of the monovalent selective cation channel, TrpM5. These events lead to membrane depolarization, action potentials and release of ATP as a transmitter to activate gustatory afferents. The Gα subunit, α-gustducin, activates a phosphodiesterase to decrease intracellular cAMP levels, although the precise targets of cAMP have not been identified. With the molecular identification of the taste GPCRs, it has become clear that taste signalling is not limited to taste buds, but occurs in many cell types of the airways. These include solitary chemosensory cells, ciliated epithelial cells and smooth muscle cells. Bitter receptors are most abundantly expressed in the airways, where they respond to irritating chemicals and promote protective airway reflexes, utilizing the same downstream signalling effectors as taste cells.

Figure 1

A. Diagrammatic illustration of a taste bud, showing the 3 types of taste cells and a renewing population of basal (B) cells. Type II cells contain the GPCRs signaling effectors for bitter, sweet, and umami stimuli, and are the focus of this review. Type I cells are generally considered to have a support function, while Type III cells respond to sour stimuli and form prominent synapses with afferent nerve fibers. Type II cells also associate closely with afferent nerve fibers, but do not form conventional synapses. B. Image of two taste buds, showing Type II cells stained with an antibody against the Type III IP3 receptor, and nerve fibers stained with an antibody against the purinergic receptor P2X2. Apical staining of P2X2 may represent non-specific binding. (Image courtesy of A. Montoya and J. Kinnamon, University of Denver).

Figure 2

Diagrammatic representation of taste GPCRs (top panel) and downstream signaling effectors (bottom panel). Receptor binding leads to Gβγ activation of PLCβ2, production of IP₃, release of Ca²⁺ from intracellular stores, Ca²⁺ dependent activation of TrpM5, depolarization, activation of voltage-gated Na⁺ channels (VGNC), and release of ATP through pannexin-1 hemichannels. The released ATP activates purinergic receptors on afferent nerve fibers. Alpha gustducin tonically regulates cAMP levels via activation of a phosphodiesterase (PDE), which subsequently prevents phosphorylation and desensitization of Ca²⁺ signaling effectors.

Figure 3

Laser scanning confocal image of two TrpM5-GFP labeled solitary chemosensory cells of the mouse nasal epithelium. Nerve endings are stained with an antibody against substance P, a transmitter expressed in peptidergic trigeminal nerve fibers. (Image courtesy of M. Tizzano, University of Colorado Denver).

Figure 4

Diagrammatic illustration of differences in signaling effectors in taste cells, SCCs of the airway, ciliated epithelial cells, and smooth muscle cells lining the airways. In all cases taste GPCRs activate the downstream PLC signaling effectors, but the effects of increased Ca²⁺ differ among the different cell types.