Transient receptor potential cation channel subfamily V member 2 is a
potassium channels
, and has similar functions throughout multiple species; recent research has also shown multiple interactions in the human body.
TRP subfamily
The vanilloid TRP subfamily (TRPV) named after the vanilloid receptor 1 consist of six members, four of them (TRPV1-TRPV4) have been related to thermal sensation. TRPV2 shares 50% of its homology with TRPV1. Compared to TRPV1 channels, TRPV2 channels do not open in response to vanilloids like
lungs, which indicates its versatile function. The channel has an important role for basic cell function including contraction, cell proliferation, and cell death. The same channel can have different functions depending on the type of tissue. Other roles of TRPV2 continue to be explored in an attempt to define the role of translocation of TRPV2 by growth factors. SET2 is a TRPV2 selective antagonist.[8]
Discovery
TRPV2 was independently discovered by two research groups and described in 1999. It was identified in the lab of
insulin-like growth factor-1
(IGF-1). Upon stimulation of cells with IGF-1, it was discovered that TRPV2 translocates towards and integrates into the cell membrane and increases intracellular calcium concentrations.
Structure
TRPV2 channel has a similar structure to
potassium channels, which are the largest ion channel family. This channel is composed of six transmembrane spanning regions (S1-S6) with a pore forming loop between S5 and S6.[9] The pore forming loop also defines the selectivity filter, which determines the ions that are able to enter the channel. The S1-S4 region, as well as the N and C terminals of the protein, is important in reference to the gating of the channel. Although TRPV2 is a nonspecific cation channel, it is more permeable to calcium ions; calcium is an intracellular messenger and plays a very important role in a variety of different cellular processes. At rest, the pore channel is closed; in the activated state, the channel opens, allowing the influx of sodium and calcium ions that initiates an action potential
.
Species homology
The TRPV subfamily of channels of 1 through 4 have unique functions. One important variation is that these channels trigger cellular signaling pathways via non-selective cation flux, making them unique. Specifically, the TRPV2 channel has structural similarities amongst the other members of the TRPV family. For instance, the channel consists of six
proteins
coded come from a common ancestor where their structures are conserved in function.
Among the subfamily, TRPV2 and TRPV1 share 50% of their sequence identity not only in humans, but in rats as well. The rat TRPV2 can be comparable to that of humans because they exhibit similar surface localization among one another. Each channel possesses
orthologues
.
Tissue distribution
Homo sapiens
In
mRNA expression of TRPV2 in mice, it is also speculated that it is expressed in arterial muscle cells, which can then be influenced by blood pressure; though it was evident that TRPV2 expression was localized in the intracellular area, some growth factors localized it to the plasma cell membrane.[11] In circulatory organs, studies and data suggest that TRPV2 may be a mechanosensor, meaning that it can sense changes in external stimuli; the mechanisms involved in opening TRPV2 by membrane stretching or hypoosmotic cell swelling have not yet been determined.[11]
Mus musculus
In
adipocytes and in brown adipose tissue (BAT). It can be concluded that TRPV2 plays a role in BAT thermogenesis in mice, since it was found that a lack of TRPV2 impairs this thermogenesis in BAT; given these results, this could be a target for human obesity therapy.[13]
Rattus norvegicus
In
adrenal glands and the lungs, being most present in the adrenal glands. TRPV2 is also present in the thymus and spleen, but not in high amounts. Without using any external growth factors, TRPV2 is highly specific to the plasma cell membrane in rat adult dorsal root ganglions, cerebral cortex, and arterial muscle cells.[11]
Clinical significance
Cancer
TRPV2 plays a role in negative homeostatic control of excess cell proliferation by inducing
apoptotic cell death, leading to harmful, carcinogenic cell survival.[18]
Immunity
TRPV2 is expressed in the spleen,
leukocytes (white blood cells) rich in histamine which are able to respond to a variety of stimuli, often initiating inflammatory and/or allergic responses. The responses generated by mast cells rely on the calcium influx in the plasma membrane with the help of channels. Surface localization of the TRPV2 protein along with coupling of the protein to calcium and proinflammatory degranulation have been found in mast cells. The activation of TRPV2 in high temperatures permits calcium ion influx, inducing the release of proinflammatory factors. Therefore, TRPV2 is essential in mast cell degranulation as a result of its response to heat.[20]
Immune cells are also able to kill pathogens by binding to them and engulfing them in a process known as
CD8+ T cells as well as in human B lymphocytes. TRPV2 is one type of ion channel that directs T cell activation, proliferation, and defense mechanisms. If the TRPV2 channel were absent or not functioning properly in T cells, T cell receptor signaling would not be optimal. TRPV2 also acts as a transmembrane protein on the surface of B cells, negatively controlling B cell activation.[20] Abnormal TRPV2 expression has been reported in hematological diseases including multiple myeloma, myelodysplastic syndrome, Burkitt lymphoma, and acute myeloid leukemia.[19]
Metabolic
TRPV2 seems to be essential in glucose
plasma membrane. This triggers the influx of calcium resulting in insulin secretion.[7]
Cardiovascular
TRPV2 is very important in the structure and function of
intercalated discs
which allows the synchronous contraction of cardiomyocytes. Abnormal expression of TRPV2 results in reduced shortening length, shortening rate, and lengthening rate which ultimately compromise cardiac contractile function.