Role of G protein-coupled receptors in vertebrate olfaction and gustation

In this article, I briefly describe the role of G protein-coupled receptors in vertebrate olfaction and gustation.

Table of Contents

G-protein coupled receptors (GPCRs)

These receptors act through a guanosine nucleotide-binding protein or G-protein family member. Signal transduction is defined through three essential components. The three essential components can be described as a plasma membrane receptor with seven transmembrane helical segments, a G-protein that cycles between active and inactive forms, and an effector enzyme in the plasma membrane. A hormone, growth factor, or neurotransmitter acts as the first messenger that activates a receptor from outside the cell. The activated receptor causes its associated G-protein to exchange its bound GDP for a GTP from the cytosol. This causes the dissociation of the G-protein from the activated receptor and binding to the nearby effector enzyme, thus altering its activity.

The human genome encodes over 800 GPCRs. Out of these, about 350 detect hormones, growth factors, and other endogenous ligands. Nearly 500 receptors serve as olfactory and gustatory receptors. GPCRs have been implicated in many human conditions, including allergies, depression, blindness, diabetes, and various cardiovascular disorders. Around 20% of all cancers involve GPCR mutations. More than one-third of the drugs in the market target one GPCR or another.

Similar mechanisms in olfaction, gustation, and vision

The sensory cells of olfaction and gustation share the same features with the visual receptor system. When an odorant molecule attaches to its specific GPCR, it triggers a change in receptor conformation. Thus, it activates a G-protein, Golf (analogous to transducin and G_S of the β-adrenergic system).

The activated G_olfactivates adenylyl cyclase, raising the local concentration of cAMP. This causes the opening of the cAMP-gated Na⁺ and Ca²⁺ channels of the plasma membrane. The influx of Na⁺ and Ca²⁺ results in a small depolarization called the receptor potential.

If an ample amount of odorant molecules encounter receptors, the receptor potential becomes strong and stimulates the neuron. The neuron in turn fires an action potential. This signal is relayed to the brain in different stages and registers as a specific smell. All these events take place within 100 to 200 ms. The absence of olfactory stimulus causes the shutdown of the transducing machinery in several ways. Golf hydrolyzes its bound GTP to GDP, thus inactivating itself. A specific kinase phosphorylates the receptor, thus preventing its interaction with G_olf . This happens by a mechanism similar to desensitizing the β-adrenergic receptor and rhodopsin.

Sense of taste in vertebrates

The clustering of gustatory neurons in taste buds on the surface of the tongue leads to the sense of taste in vertebrates. Sweet-tasting molecules bind receptors in “ sweet” taste buds. GPCRs are coupled to the heterotrimeric G protein gustducin. The binding of the tastant molecule to its receptor activates gustducin and stimulates the production of cAMP by adenyl cyclase. cAMP concentration increases to activate PKA, which phosphorylates K⁺ channels in the plasma membrane, causing them to close and sending an electrical signal to the brain. Other taste buds detect bitter, sour, salty, or savory tastants, using various combinations of second messengers and ion channels in the transduction mechanisms.

Common features of signaling systems detecting hormones, light, smell, and taste

Signal transducing systems act through heterotrimeric G proteins share common features that show their evolutionary relations (figure 1). The receptors consist of seven transmembrane segments, a domain interacting with G protein, and a carboxy-terminal cytoplasmic domain that undergoes reversible phosphorylation on various Ser and Thr residues. The ligand binding site is placed deep inside the membrane and includes residues from several of the transmembrane segments. The receptor undergoes a conformational change after ligand binding, exposing an interacting domain with a G-protein. Heterotrimeric G proteins activate or inhibit effector enzymes adenylyl cyclase, Phosphodiesterases (PDE), and phospholipase C (PLC). These enzymes change the concentration of a second messenger cAMP, cGMP, IP₃, or Ca²⁺(figure 1).

**Figure 1: signaling systems that detect hormones, light, smells, and tastes**

In the hormone-detecting systems, the final output is an activated protein kinase that phosphorylates a protein critical to that process. In sensory neurons, the output involves a change in membrane potential and a consequent electrical signal that passes to another neuron in the pathway to the brain.

All these signaling systems inactivate themselves. The intrinsic GTPase activity of G proteins converts the bound GTP to GDP, often augmented by GTPase activating proteins (GAP proteins) or regulators of G-protein signaling (RGS proteins). Each of the 1000 G-protein coupled receptors of vertebrates is selectively expressed in certain cell types and under some conditions. Together, they allow cells and tissues to respond to a wide range of stimuli, including low molecular weight amines, peptides, proteins, lipids, and many compounds detected by olfaction and gustation. The two receptors, the β-adrenergic receptor, and the histamine receptor are the targets of a variety of widely used beta-blockers and antihistamine mediators respectively.

Conclusion

G-protein coupled receptors act through a member of the guanosine nucleotide-binding protein or G-protein, family. Signal transduction is defined through three essential components. The three essential components can be described as a plasma membrane receptor with seven transmembrane helical segments, a G-protein that cycles between active and inactive forms, and an effector enzyme in the plasma membrane.

The sensory cells of olfaction and gustation share the same features with the visual receptor system. When an odorant molecule attaches to its specific GPCR, it triggers a change in receptor conformation. Thus, it activates a G-protein, G_olf (analogous to transducin and G_S of the β-adrenergic system).

The clustering of gustatory neurons in taste buds on the surface of the tongue leads to the sense of taste in vertebrates. Sweet-tasting molecules bind receptors in “ sweet” taste buds. GPCRs are coupled to the heterotrimeric G protein gustducin. Other taste buds detect bitter, sour, salty, or savory tastants, using various combinations of second messengers and ion channels in the transduction mechanisms.

Signal transducing systems act through heterotrimeric G proteins that share common features that show their evolutionary relations. The receptors consist of seven transmembrane segments, a domain interacting with G protein, and a carboxy-terminal cytoplasmic domain that undergoes reversible phosphorylation on various Ser and Thr residues.

Each of the 1000 G-protein coupled receptors of vertebrates is selectively expressed in certain cell types and under some conditions. Together, they allow cells and tissues to respond to a wide range of stimuli, including low molecular weight amines, peptides, proteins, lipids, and many compounds detected by olfaction and gustation.