Transient receptor potential channel
[2][3][4] Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of taste, pressure, and vision.
In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold.
[6][7] These ion channels have a relatively non-selective permeability to cations, including sodium, calcium and magnesium.
Mammalian TRP channels are activated and regulated by a wide variety of stimuli and are expressed throughout the body.
[13] Comparative studies have shown that the functional domains and critical amino acids of TRPM channels are highly conserved across species.
[16] TRPN was originally described in Drosophila melanogaster and Caenorhabditis elegans as nompC, a mechanically gated ion channel.
[22][21] Only a single TRPN, N for "no mechanoreceptor potential C," or "nompC", is known to be broadly expressed in animals (although some Cnidarians have more), and is notably only a pseudogene in amniote vertebrates.
[21][11] Despite TRPA being named for ankyrin repeats, TRPN channels are thought to have the most of any TRP channel, typically around 28, which are highly conserved across taxa [21] Since its discovery, Drosophila nompC has been implicated in mechanosensation (including mechanical stimulation of the cuticle and sound detection) and cold nociception.
Mechanistic studies of these latter clades have been largely restricted to Drosophila, but phylogenetic analyses has placed a number of other genes from Placozoa, Annelida, Cnidaria, Mollusca, and other arthropods within them.
[11] TRPVL has been proposed to be a sister clade to TRPV, and is limited to the cnidarians Nematostella vectensis and Hydra magnipapillata, and the annelid Capitella teleta.
Patch clamp techniques and hyperosmotic stimulation have illustrated that TRPY plays a role in intracellular calcium release.
Mammalian TRP channels are activated and regulated by a wide variety of stimuli including many post-transcriptional mechanisms like phosphorylation, G-protein receptor coupling, ligand-gating, and ubiquitination.
The ion selectivity filter, pore, is formed by the complex combination of p-loops in the tetrameric protein, which are situated in the extracellular domain between the S5 and S6 transmembrane segments.
Starting from the intracellular N-terminus there are varying lengths of ankryin repeats (except in TRPM) that aid with membrane anchoring and other protein interactions.
Shortly following S6 on the C-terminal end, there is a highly conserved TRP domain (except in TRPA) which is involved with gating modulation and channel multimerization.
[8][13][12] TRP channels modulate ion entry driving forces and Ca2+ and Mg2+ transport machinery in the plasma membrane, where most of them are located.
In the body, some TRP channels are thought to behave like microscopic thermometers and are used in animals to sense hot or cold.
[38] Thermo-TRP channels have a C-terminal domain that is responsible for thermosensation and have a specific interchangeable region that allows them to sense temperature stimuli that is tied to ligand regulatory processes.
Several other TRP channels play a significant role in chemosensation through sensory nerve endings in the mouth that are independent from taste buds.
Variations in light intensity affect the total number of open TRP/TRPL channels, and, therefore, the degree of membrane depolarization.
Excitation of rhodopsin in mammalian photoreceptors leads to the hyperpolarization of the receptor membrane but not to depolarization as in the insect eye.
In Drosophila and, it is presumed, other insects, a phospholipase C (PLC)-mediated signaling cascade links photoexcitation of rhodopsin to the opening of the TRP/TRPL channels.
TRPV1 expression in aggregates found at endoplasmic reticulum or Golgi apparatus and/or surrounding these structures in breast cancer patients confer worse survival.
[49] In addition to TLR4 mediated pathways, certain members of the family of the transient receptor potential ion channels recognize LPS.
[51] At higher concentrations, LPS activates other members of the sensory TRP channel family as well, such as TRPV1, TRPM3 and to some extent TRPM8.
[36] It was investigated subsequently by Baruch Minke, a post-doc in the group of William Pak, and named TRP according to its behavior in the ERG.
[54] The identity of the mutated protein was unknown until it was cloned by Craig Montell, a post-doctoral researcher in Gerald Rubin's research group, in 1989, who noted its predicted structural relationship to channels known at the time[37] and Roger Hardie and Baruch Minke who provided evidence in 1992 that it is an ion channel that opens in response to light stimulation.
[56] In 2013, Montell and his research group found that the TRPL (TRP-like) cation channel was a direct target for tastants in gustatory receptor neurons and could be reversibly down-regulated.
- TRPC5 overexpression activates the transcription factor NFATC3 Ca 2+ signaling pathway, leading to p-gp overexpression. Moreover, the overexpressed p-gp expels chemotherapeutic drugs such as doxorubicin triggering chemoresistance.
- Chemoresistant breast cancer cells overexpressing TRPC5 transfer channel units to chemo sensitive recipient cells via extracellular vesicles (EV), leading to the development of TRPC5-mediated chemoresistance in these cells. [ 49 ]