Trace amine-associated receptors (TAARs), sometimes referred to as trace amine receptors (TAs or TARs), are a family of G protein-coupled receptors that were discovered in 2001. TAARs are mainly known for two functions, originally via studies of humans and mammals:
TAAR2–TAAR9 work as olfactory receptors expressed by sensory neurons in the main olfactory epithelium, tuned to detect volatile amine odorants. TAAR1 primarily works as an intracellular receptor, detecting endogenous trace amines phenethylamine, tyramine, and tryptamine – metabolic derivatives of the amino acids phenylalanine, tyrosine and tryptophan, respectively – ephedrine, as well as the synthetic psychostimulants, amphetamine, methamphetamine and methylenedioxymethamphetamine (MDMA, ecstasy). Their localization in the central nervous system has garnered considerable interest in academic and proprietary pharmaceutical research. In 2004, it was shown that mammalian TAAR1 is also a receptor for thyronamines, decarboxylated and deiodinated relatives of thyroid hormones. TAARs form a sister clade to a family of receptors not found in the aminotes but widely distributed in the other vertebrates called TAAR-like (TARL). TAAR and TARL are vertebrate inventions, originally arising via a duplication of the 5-HT4 receptor (htr4). The jawed fish adapted TAAR to the role of olfaction while the jawless fish independently adapted TARL into the same role. TAAR-TARL is only one of the four gene families commonly used for olfaction in vertebrates; in humans, most olfactory receptors belong to the OR family.
Animal TAAR complement
Count The following is a list of the number of TAARs contained in selected animal genomes:
Tetrapods Mammals Human – 6 genes (TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, TAAR9) and 3 pseudogenes (TAAR3P, TAAR4P, TAAR7P) Chimpanzee – 3 genes (1, 5, 6) and 6 pseudogenes (2–4P, 7–9P) Mouse – 15 genes (1–6, 7a–b, 7d–f, 8a–c, 9) and 1 pseudogene (7cP) Rat – 17 genes (1× 1–6 and 9; 7× 7, 3× 8) and 2 pseudogenes (2× 7P) Amphibian: Pipid frog – 7 genes and 0 pseudogenes (TARL, TAAR1, 5× TAAR4) Ray-finned fish: Zebrafish – 112 genes and 4 pseudogenes Medaka – 25 genes and 1 pseudogenes Stickleback – 25 genes and 1 pseudogenes In most vertebrates, TAARs occur as a conserved gene cluster.
Classification
Vertebrate TAARs are phylogenetically resolved into two classes, which can be further broken down into subclades. Tetrapods (amphibians, mammals, birds, lizards, etc.) have TAARs from three subclades: A3 (mammalian TAAR1), B1 (TAAR2–4), and B3 (TAAR5–9), in which only the class II TAARs play a role in olfaction. Fish taar12 is B1 and taar13 is B3. The subclade B4 (formerly "class III") originated in the ray-finned fishes from a duplication of taar13 and subsequently expanded. TARL is not an olfactory receptor in bony vertebrates. The zebrafish tarl1 gene is minimally expressed in the nose but highly expressed int he brain, indicating a TAAR1-like role. Older literature use a more complicated, somewhat chaotic, classification. For example, due to narrower taxonomic sampling, the TARL of bony vertebrates were thought to form a separate clade from TARL called "class V". There are many such extra splits that need to be re-interpreted by comparing them against a modern tree.
Human trace amine-associated receptors Six human trace amine-associated receptors (hTAARs) – hTAAR1, hTAAR2, hTAAR5, hTAAR6, hTAAR8, and hTAAR9 – have been identified and partially characterized. The table below contains summary information from literature reviews, pharmacology databases, and supplementary primary research articles on the expression profiles, signal transduction mechanisms, ligands, and physiological functions of these receptors.
Disease links and clinical significance Ulotaront / SEP 363856 is a TAAR1 agonist in phase 3 clinical trials for schizophrenia and earlier trials for Parkinson's Disease psychosis. The medicine has obtained Breakthrough designation from the US FDA.
See also Olfactory receptor Odorant Pheromone Pheromone receptor Psychostimulant Thyronamine Trace amine
References
External links "Trace Amine Receptors". The International Union of Basic and Clinical Pharmacology, The British Pharmacological Society, The University of Edinburgh. International Union of Basic and Clinical Pharmacology. Additional database mappings:
IPR009133 (PR01830) - TAAR1 cd15314 - TAAR1