Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a
protein that in humans is encoded by the ''TRPM2''
gene.
Structure
The protein encoded by this gene is a non-selective calcium-permeable
cation channel and is part of the
Transient Receptor Potential ion channel super family. The closest relative is the cold and
menthol
Menthol is an organic compound, more specifically a monoterpenoid, made synthetically or obtained from the oils of corn mint, peppermint, or other mints. It is a waxy, clear or white crystalline substance, which is solid at room temperature and ...
activated
TRPM8 ion channel. While TRPM2 is not cold sensitive it is activated by heat.
The TRPM2 ion channel is activated by free intracellular
ADP-ribose in synergy with free intracellular
calcium.
ADP-Ribose is produced to by the enzyme
PARP in response to oxidative stress and confers susceptibility to
cell death. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.
Function
The ''TRPM2'' gene is highly expressed in the brain and was implicated by both genetic linkage studies in families
and then by case control or trio allelic association studies in the genetic aetiology of
bipolar affective disorder (Manic Depression).
The physiological role of TRPM2 is not well understood. It was shown to be involved in
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
secretion.
In the
immune cells it mediates parts of the responses to
TNF-alpha.
A role has been suggested for TRPM2 in activation of
NLRP3 inflammasome, the dysregulation of which is strongly associated with a number of auto inflammatory and metabolic diseases, such as gout, obesity and diabetes.
In the brain it is involved in the toxicity of
amyloid beta
Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...
, a protein associated with
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
.
In 2016, TRPM2 channel was strongly implicated in the detection of non-painful warm stimuli. Chun-Hsiang Tan and Peter McNaughton studied the responses of actual sensory neurons to thermal stimuli, then used an RNA-sequencing strategy to identify TRPM2 as genetically required for warmth detection in the non-noxious range of 33–38 °C.
Clinical significance
TRPM2 expression and function help preserve cancer cell viability.
TRPM2 channels are highly expressed in many cancers, notably
neuroblastoma.
See also
*
TRPM
References
Further reading
*
*
External links
*
{{Transient receptor potential channel modulators
Ion channels
Biology of bipolar disorder
Nudix hydrolases