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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''TAAR2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
TAAR2 is coexpressed 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 series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
mechanisms have not been determined.
Tissue distribution
Human TAAR2 (hTAAR2) is expressed in the
cerebellum
The cerebellum (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 or even larger. In humans, the cerebe ...
,
olfactory sensory neurons in the
olfactory epithelium
The olfactory epithelium is a specialized epithelial tissue inside the nasal cavity that is involved in smell. In humans, it measures
9 cm2 and lies on the roof of the nasal cavity about 7 cm above and behind the nostrils. The olfactory ...
, and
leukocyte
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
s (i.e., white blood cells), among other tissues.
hTAAR1 and hTAAR2 are both required for white blood cell activation by
trace amines
Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to the ...
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. They ha ...
.
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 ...
, but intensive staining was found in the deeper layer as well. The histochemical reaction was observed in the fibers of the
olfactory nerve
The olfactory nerve, also known as the first cranial nerve, cranial nerve I, or simply CN I, is a cranial nerve that contains sensory nerve fibers relating to the sense of smell.
The afferent nerve fibers of the olfactory receptor neurons t ...
, 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
The piriform cortex, or pyriform cortex, is a region in the brain, part of the rhinencephalon situated in the cerebrum. The function of the piriform cortex relates to the sense of smell.
Structure
The piriform cortex is part of the rhinencepha ...
molecular area,
hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic syste ...
(
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
In neuroanatomy, the postcentral gyrus is a prominent gyrus in the lateral parietal lobe of the human brain. It is the location of the primary somatosensory cortex, the main sensory receptive area for the somatosensory system, sense of touch. Lik ...
of the
cortex (layer 5). Real-time quantitative PCR with reverse transcription confirmed TAAR2 gene expression in the mouse brain areas such as the
frontal cortex
The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove be ...
,
hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus ...
, 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 ...
.
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. Dopamine constitutes about 80% o ...
in the
striatum
The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives gluta ...
tissue than wild-type littermates and lower level of
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...
in
hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic syste ...
. Also, they have lower levels of
MAO-B expression in
midbrain
The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal ( alertness), and temperature regulation. The name comes from the Greek ''mesos'', ...
and
striatum
The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives gluta ...
. A significantly higher number of the
dopamine neurons
Dopaminergic pathways (dopamine pathways, dopaminergic projections) in the human brain are involved in both physiological and behavioral processes including movement, cognition, executive functions, reward, motivation, and neuroendocrine control. ...
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 ap ...
pars compacta. TAAR2 knockout mice have significantly higher level of horizontal activity and lower immobilization time in
forced swim test
The behavioural despair test (or Porsolt forced swimming test) is a test, centered on a rodent's response to the threat of drowning, whose result has been interpreted as measuring susceptibility to negative mood. It is commonly used to measure the ...
.
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
The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute t ...
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 canon ...
(
BDNF) level in the
striatum
The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives gluta ...
.
A
single nucleotide polymorphism
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
nonsense mutation of the TAAR2 gene is associated with
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social w ...
.
TAAR2 is a probable
pseudogene
Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes ar ...
in 10–15% of Asians as a result of a
polymorphism that produces a
premature stop codon
In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a ''nonsense codon'' in the transcribed mRNA, and in leading to a truncated, incomplete, and usually nonfunctional protein produ ...
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‐iodo‐thyronamine(T1AM) was identified as a nonselective ligand for TAAR2.
Addditional TAAR1 ligands, p-tyramine and Beta-phenylethylamine(2-PEA) trigger TAAR2 dependant actions, though direct binding has not been demonstrated.
See also
*
Trace amine
Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to th ...
*
Trace amine-associated receptor
References
G protein-coupled receptors
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