Trace amine-associated receptor 2 (TAAR2), formerly known as G protein-coupled receptor 58 (GPR58), is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''TAAR2''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
TAAR2 is co-expressed with
Gα proteins;
however, its
signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...
mechanisms have not been determined.
Tissue distribution
Human TAAR2 (hTAAR2) is expressed in the
cerebellum
The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...
,
olfactory sensory neurons in the
olfactory epithelium
The olfactory epithelium is a specialized epithelium, epithelial tissue inside the nasal cavity that is involved in olfaction, smell. In humans, it measures
and lies on the roof of the nasal cavity about above and behind the nostrils. The olfact ...
, and
leukocytes (i.e., white blood cells), among other tissues.
hTAAR1 and hTAAR2 are both required for white blood cell activation by
trace amines in
granulocytes
Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear, that ...
.
Using brain histochemistry staining of mice with LacZ insertion into TAAR2 gene histochemical reaction was found in the glomerular layer of the
olfactory bulb
The olfactory bulb (Latin: ''bulbus olfactorius'') is a neural structure of the vertebrate forebrain involved in olfaction, the sense of smell. It sends olfactory information to be further processed in the amygdala, the orbitofrontal cortex (OF ...
, but intensive staining was found in the deeper layer as well. The histochemical reaction was observed in the fibers of the
olfactory nerve, in the glomeruli of the glomerular layer, several short axon (SA) cells (outer plexiform layer or granular layer) and neuronal projections that were visualized throughout the depth of the olfactory bulb. Furthermore, LacZ staining was observed in the limbic areas of the brain receiving olfactory input, i.e.,
piriform cortex molecular area,
hippocampus
The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...
(
CA1 field, pyramidal layer),
hypothalamic lateral zone (zone incerta) and lateral
habenula. In addition, a histochemical reaction was found in the midbrain
raphe nuclei and primary
somatosensory area of the
cortex
Cortex or cortical may refer to:
Biology
* Cortex (anatomy), the outermost layer of an organ
** Cerebral cortex, the outer layer of the vertebrate cerebrum, part of which is the ''forebrain''
*** Motor cortex, the regions of the cerebral cortex i ...
(layer 5). Real-time quantitative PCR with reverse transcription confirmed TAAR2 gene expression in the mouse brain areas such as the
frontal cortex,
hypothalamus
The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
, and
brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...
.
Involvement in the functioning of monoamine systems
TAAR2
knockout mice
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
have significantly higher level of
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
in the
striatum
The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
tissue than wild-type littermates and lower level of
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
in
hippocampus
The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...
. Also, they have lower levels of
MAO-B expression in
midbrain
The midbrain or mesencephalon is the uppermost portion of the brainstem connecting the diencephalon and cerebrum with the pons. It consists of the cerebral peduncles, tegmentum, and tectum.
It is functionally associated with vision, hearing, mo ...
and
striatum
The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
. A significantly higher number of the
dopamine neurons was detected in TAAR2-KO mice in the
substantia nigra
The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra a ...
pars compacta. TAAR2 knockout mice have significantly higher level of horizontal activity and lower immobilization time in
forced swim test.
Involvement in adult neurogenesis
It has been found that TAAR2 knockout mice have an increased number of neuroblast-like and proliferating cells in both subventricular and subgranular zones of the
dentate gyrus in comparison to wild type animals. Furthermore, TAAR2 knockout mice have an increased the
brain-derived neurotrophic factor
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the can ...
(
BDNF
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...
) level in the
striatum
The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
.
A
single nucleotide polymorphism nonsense mutation of the TAAR2 gene is associated with
schizophrenia
Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
.
TAAR2 is a probable
pseudogene
Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Pseudogenes can be formed from both protein-coding genes and non-coding genes. In the case of protein-coding genes, most pseudogenes arise as superfluous copies of fun ...
in 10–15% of Asians as a result of a
polymorphism that produces a
premature stop codon at amino acid 168.
Involvement in immune cell migration and function
TCells, B Cells and Peripheral Mononuclear cells express TAAR2 mRNA. Migration toward TAAR1 ligands required both TAAR1 and TAAR2 expression based on siRNA experiments.
In T cells, the same stimuli triggered cytokine secretion while in B cells Immunoglobulin secretion is triggered.
Possible Ligands
3‐Iodothyronamine (T1AM) was identified as a
non-selective ligand for TAAR2.
Additional TAAR1 ligands,
tyramine and
phenethylamine trigger TAAR2 dependant actions, though direct binding has not been demonstrated.
See also
*
Trace amine
*
Trace amine-associated receptor
Trace amine-associated receptors (TAARs), sometimes referred to as trace amine receptors (TAs or TARs), are a class of G protein-coupled receptors that were discovered in 2001. TAAR1, the first of six functional human TAARs, has gained considerab ...
References
G protein-coupled receptors
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