TRP/TRPV Channel

Transient receptor potential (TRP) channels are wildly expressed on the plasma membrane in numerous types of cells, including neurons. TRP superfamily is based on the differences in their amino acid sequences and topological structures, while it is difficult to differentiate the function of individual family and member simply according to the classification.  Once activated, TRP channels, with homo- or hetero- tetrameric configurations, function as an integrator of several signaling pathways to elicit a serial of responses. Thermally activated TRPs belong to members of the TRPV, TRPM, and TRPA subfamilies, while regulated exocytosis stimulates cation influx via several TRPC, TRPV, and TRPM channels.  TRPVs, activated by vanillin, vanillic acid, and capsaicin in the plants, are thermo-TRP channels, as TRPV1, TRPV2, TRPV3, and TRPV4 can be activated by heat. There are six different members (TRPV1–6) in this family. 
TRPV1 is potentiated by a decrease in PIP2 levels and PKC-mediated phosphorylation of the channel, both following PLC activation induced by proalgesic agents such as bradykinin and nerve growth factor. Activation by heat is also a feature of TRPV2, TRPV3, and TRPV4. TRPV2–4 are also polymodally activated and are capable of integrating various stimuli. TRPV2 function is upregulated by phosphatidylinositol-3-kinase activation and hypotonicity-induced cell swelling. TRPV3 is activated in cultured cells by PLC stimulation; by application of PUFAs such as arachidonic acid; by menthol; and by compounds present in spices such as oregano, cloves, and thymes. Glycosylation in the pore loop and interactions with proteins called PACSINs (involved in synaptic vesicle trafficking) regulate the surface expression of TRPV4. Insertion of TRPV5 and TRPV6 into the plasma membrane regulates their activity as well. Retention of TRPV5 in the plasma membrane is promoted by the β-glucuronidase Klotho through hydrolysis of extracellular sugar residues on the channel.


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