TRPC2

The mammalian genome encodes seven TRPCs, of which TRPC2 is the largest with the most restricted expression pattern and has several alternatively spliced variants. TRPC2 is unique among TRPCs in that its complete gene has been lost from the genomes of Old World monkeys and humans. Its still detectable genomic remnants represent a pseudogene (Yildirim E et al. 2007).

In mice, TRPC2 has been detected at the protein level in erythroblasts, spermatozoa, and brain. Its activation by erythropoietin has been described in detail. Furthermore, inhibition by Ca(2+)-calmodulin has been reported (Miller BA 2014).

The main demonstrated functions of TRPC2 are the regulation of pheromone-evoked signaling in the mouse olfactory system, the regulation of erythropoietin-stimulated calcium influx in mouse erythroid cells, and ZP3-evoked calcium influx in spermatozoa. In animal experiments, TRPC2-depleted erythrocytes were found to be resistant to oxidative stress-induced hemolysis (Hirschler-Laszkiewicz I et al. 2012; Miller BA 2014).

TRP channels are phylogenetically early signaling pathways (they can already be detected in yeast cells). The first TRP channel was identified in 1989 in connection with visual perception in Drosophila melanogaster. In a Drosophila mutant (trp343), it was shown that its photoreceptors responded to light stimuli only with a transient, i.e. rapidly inactivating, membrane current. In the non-mutated wild type, however, the current flow persisted as long as light hit the photoreceptor. The mutant protein -TRP- was cloned in 1989. Thus, the name "transient receptor potential" - TRP- refers to the description of a phenotype of a mutant of the fruit fly Drosophila melanogaster. TRP channels exert important functions in primary signaling pathways for the regulated influx of Ca2+ into a cell in both vertebrates and non-vertebrates. TRP channels in humans play an important role in the sensation of different types of taste (sweet, bitter, umami) as well as in the perception of pain, heat, warmth or cold, pressure and light. It is believed that some TRP channels in the body behave like microscopic thermosensors. To date, 28 TRP channel genes have been identified in mammals (Nilius B et al. 2011). The TRPC subfamily consists of seven members (TRPC1-7) known to be non-selective cation channels with permeability to Ca2+, Na+ and K+. Like the other members of the TRP superfamily, they contain six transmembrane domains with an ion channel between the fifth and sixth domains. The N- and C-termini of TRPCs harbor a variety of functional domains including ankyrin repeats, calmodulin binding sites, phosphorylation sites, and sites of interaction with other molecules such as Homer, Orai, STIM1, Junctate, IP3 receptor (IP3R).

1. Ahmmed GU et al (2010) Protein kinase Calpha phosphorylates the TRPC1 channel and regulates store-operated Ca2+ entry in endothelial cells. The Journal of biological chemistry
2. Hirschler-Laszkiewicz I et al (2012) Trpc2 depletion protects red blood cells from oxidative stress-induced hemolysis. Exp Hematol 40:71-83.
3. Lessard CB et al (2005) The overexpression of presenilin2 and Alzheimer's disease-linked presenilin2 variants influences TRPC6-enhanced Ca2+ entry into HEK293 cells. Cell Signal 17: 437-445.
4. Miller BA (2014) TRPC2. Handb Exp Pharmacol 222:53-65.
5. Nilius B et al (2011) The transient receptor potential family of ion channels. Genome Biol 12:218.
6. Nilius B et al. 2007). Transient receptor potential cation channels in disease. Physiol Rev 87: 165-217.
7. Yildirim E et al. (2007) TRPC2: molecular biology and functional importance. Handb Exp Pharmacol 179:53-75.
8. Zufall F (2005) The TRPC2 ion channel and pheromone sensing in the accessory olfactory system. Naunyn Schmiedebergs Arch Pharmacol 371:245-250.
9. Zufall F et al (2005) Neurobiology of TRPC2: from gene to behavior. Ploughman's Arch 451:61-71.