G protein-coupled receptor

G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors (GPLR), constitute a large protein family of receptors that detect molecules outside the cell and activate internal signal transduction pathways and, ultimately, cellular responses.

Structure

GPCRs are integral membrane proteins that possess seven transmembrane domains. The extracellular parts of the receptor can be glycosylated. These extracellular loops also contain two highly conserved cysteine residues which build disulfide bonds to stabilize the receptor structure. Some of the GPCRs also possess an extracellular N-terminus domain which binds the ligand, for example, the rhodopsin family of GPCRs.

Function

GPCRs are involved in a wide variety of physiological processes. Some examples of their physiological roles include:

• The visual sense: The photoreceptor cells in the retina possess the photoreceptor protein, which is a GPCR. The opsin in these proteins undergoes a conformational change when it absorbs a photon, leading to a series of events which ends in an electrical signal being sent to the brain.
• The gustatory sense (taste): GPCRs in taste cells mediate release of intracellular calcium, allowing the cell to release neurotransmitters into the synaptic cleft.
• The sense of smell: Receptors of the olfactory epithelium bind odorants, and, here again, use GPCRs to produce an electrical signal.
• Behavioral and mood regulation: Receptors in the mammalian brain bind several different neurotransmitters, including serotonin, dopamine, GABA, and glutamate.
• Regulation of immune system activity and inflammation: Chemokine receptors bind ligands that mediate intercellular communication between cells of the immune system. GPCRs are also involved in immune-modulation and directly involved in suppression of TLR-induced immune responses from T cells.

Classification

GPCRs are classified by the International Union of Basic and Clinical Pharmacology (IUPHAR) into several families, based on sequence homology:

• Class A (or 1) (Rhodopsin-like)
• Class B (or 2) (Secretin receptor family)
• Class C (or 3) (Metabotropic glutamate/pheromone)
• Class D (or 4) (Fungal mating pheromone receptors)
• Class E (or 5) (Cyclic AMP receptors)
• Class F (or 6) (Frizzled/Smoothened)

See also

• Adrenergic receptor
• Dopamine receptor
• Histamine receptor
• Serotonin receptor
• Metabotropic glutamate receptor