Skip to main content
Springer Nature Link
Log in

TRPC2

  • Chapter
  • First Online:
Mammalian Transient Receptor Potential (TRP) Cation Channels

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 222))

  • 8748 Accesses

Abstract

Trp2 was the second ortholog of the Drosophila trp gene to be identified. Whereas full-length TRPC2 transcripts have been cloned in a number of species including mice, rats, and New World monkeys, TRPC2 is a pseudogene in humans, apes, Old World monkeys, and in a number of other vertebrates. TRPC2 is highly expressed in the rodent VNO. It is also detectable at the protein level in murine erythroblasts, sperm, and brain and has been detected in other tissues by RT-PCR. Its activation by DAG and by erythropoietin has been described in greatest detail, and inhibition by Ca2+-calmodulin has been reported. The major demonstrated functions of TRPC2 are regulation of pheromone-evoked signaling in the rodent VNO, regulation of erythropoietin-stimulated calcium influx in murine erythroid cells, and ZP3-evoked calcium influx into sperm. Depletion of TRPC2 in knockout mice resulted in changes in behavior including altered sex discrimination and lack of male–male aggression. The red cells of TRPC2 knockout mice showed increased mean corpuscular volume, mean corpuscular hemoglobin, and hematocrit and reduced mean corpuscular hemoglobin concentration. TRPC2-depleted red cells were resistant to oxidative stress-induced hemolysis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (Canada)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (Canada)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (Canada)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Amer J, Ghoti H, Rachmilewitz E, Koren A, Levin C, Fibach E (2006) Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants. Br J Haematol 132:108–113

    Article  PubMed  CAS  Google Scholar 

  • Balzer M, Lintschinger B, Groschner K (1999) Evidence for a role of Trp proteins in the oxidative stress-induced membrane conductances of porcine aortic endothelial cells. Cardiovasc Res 42:543–549

    Article  PubMed  CAS  Google Scholar 

  • Bogdanova A, Makhro A, Wang J, Lipp P, Kaestner L (2013) Calcium in red blood cells-a perilous balance. Int J Mol Sci 14:9848–9872

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Cai X, Patel S (2010) Degeneration of an intracellular ion channel in the primate lineage by relaxation of selective constraints. Mol Biol Evol 27:2352–2359

    Article  PubMed  CAS  Google Scholar 

  • Chu X, Cheung JY, Barber DL, Birnbaumer L, Rothblum LI, Conrad K, Abrasonis V, Chan YM, Stahl R, Carey DJ et al (2002) Erythropoietin modulates calcium influx through TRPC2. J Biol Chem 277:34375–34382

    Article  PubMed  CAS  Google Scholar 

  • Chu X, Tong Q, Cheung JY, Wozney J, Conrad K, Mazack V, Zhang W, Stahl R, Barber DL, Miller BA (2004) Interaction of TRPC2 and TRPC6 in erythropoietin modulation of calcium influx. J Biol Chem 279:10514–10522

    Article  PubMed  CAS  Google Scholar 

  • Chu X, Tong Q, Wozney J, Zhang W, Cheung JY, Conrad K, Mazack V, Stahl R, Barber DL, Miller BA (2005) Identification of an N-terminal TRPC2 splice variant which inhibits calcium influx. Cell Calcium 37:173–182

    Article  PubMed  CAS  Google Scholar 

  • Clark MR, Mohandas N, Shohet SB (1980) Deformability of oxygenated irreversibly sickled cells. J Clin Invest 65:189–196

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Foller M, Huber SM, Lang F (2008) Erythrocyte programmed cell death. IUBMB Life 60:661–668

    Article  PubMed  CAS  Google Scholar 

  • Frankenberg S, Schneider NY, Fletcher TP, Shaw G, Renfree MB (2011) Identification of two distinct genes at the vertebrate TRPC2 locus and their characterisation in a marsupial and a monotreme. BMC Mol Biol 12:39

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gillo B, Ma YS, Marks AR (1993) Calcium influx in induced differentiation of murine erythroleukemia cells. Blood 81:783–792

    PubMed  CAS  Google Scholar 

  • Grus WE, Zhang J (2009) Origin of the genetic components of the vomeronasal system in the common ancestor of all extant vertebrates. Mol Biol Evol 26:407–419

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hasen NS, Gammie SC (2009) Trpc2 gene impacts on maternal aggression, accessory olfactory bulb anatomy and brain activity. Genes Brain Behav 8:639–649

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hensold JO, Dubyak G, Housman DE (1991) Calcium ionophore, A23187, induces commitment to differentiation but inhibits the subsequent expression of erythroid genes in murine erythroleukemia cells. Blood 77:1362–1370

    PubMed  CAS  Google Scholar 

  • Hirschler-Laszkiewicz I, Zhang W, Keefer K, Conrad K, Tong Q, Chen SJ, Bronson S, Cheung JY, Miller BA (2012) Trpc2 depletion protects red blood cells from oxidative stress-induced hemolysis. Exp Hematol 40:71–83

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hoenderop JG, Voets T, Hoefs S, Weidema F, Prenen J, Nilius B, Bindels RJ (2003) Homo- and heterotetrameric architecture of the epithelial Ca2+ channels TRPV5 and TRPV6. EMBO J 22:776–785

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hofmann T, Schaefer M, Schultz G, Gudermann T (2000) Cloning, expression and subcellular localization of two novel splice variants of mouse transient receptor potential channel 2. Biochem J 351:115–122

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hofmann T, Schaefer M, Schultz G, Gudermann T (2002) Subunit composition of mammalian transient receptor potential channels in living cells. Proc Natl Acad Sci USA 99:7461–7466

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Jungnickel MK, Marrero H, Birmbaumer L, Lémos JR, Florman HM (2001) Trp2 regulates entry of Ca2+ into mouse sperm triggered by egg ZP3. Nat Cell Biol 3:499–502

    Article  PubMed  CAS  Google Scholar 

  • Kato A, Touhara K (2009) Mammalian olfactory receptors: pharmacology, G protein coupling and desensitization. Cell Mol Life Sci 66:3743–3753

    Article  PubMed  CAS  Google Scholar 

  • Kieran MW, Perkins AC, Orkin SH, Zon LI (1996) Thrombopoietin rescues in vitro erythroid colony formation from mouse embryos lacking the erythropoietin receptor. Proc Natl Acad Sci USA 93:9126–9131

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kim S, Ma L, Jensen KL, Kim MM, Bond CT, Adelman JP, Yu CR (2012) Paradoxical contribution of SK3 and GIRK channels to the activation of mouse vomeronasal organ. Nat Neurosci 15:1236–1244

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kiselyov K, van Rossum DB, Patterson RL (2010) TRPC channels in pheromone sensing. Vitam Horm 83:197–213

    Article  PubMed  CAS  Google Scholar 

  • Lang KS, Duranton C, Poehlmann H, Myssina S, Bauer C, Lang F, Wieder T, Huber SM (2003) Cation channels trigger apoptotic death of erythrocytes. Cell Death Differ 10:249–256

    Article  PubMed  CAS  Google Scholar 

  • Leypold BG, Yu CR, Leinders-Zufall T, Kim MM, Zufall F, Axel R (2002) Altered sexual and social behaviors in trp2 mutant mice. Proc Natl Acad Sci USA 99:6376–6381

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Liman ER, Innan H (2003) Relaxed selective pressure on an essential component of pheromone transduction in primate evolution. Proc Natl Acad Sci USA 100:3328–3332

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Liman ER, Corey DP, Dulac C (1999) TRP2: a candidate transduction channel for mammalian pheromone sensory signaling. Proc Natl Acad Sci USA 96:5791–5796

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lin CS, Lim SK, D'Agati V, Costantini F (1996) Differential effects of an erythropoietin receptor gene disruption on primitive and definitive erythropoiesis. Genes Dev 10:154–164

    Article  PubMed  CAS  Google Scholar 

  • Lucas P, Ukhanov K, Leinders-Zufall T, Zufall F (2003) A diacylglycerol-gated cation channel in vomeronasal neuron dendrites is impaired in TRPC2 mutant mice: mechanism of pheromone transduction. Neuron 40:551–561

    Article  PubMed  CAS  Google Scholar 

  • Mast TG, Brann JH, Fadool DA (2010) The TRPC2 channel forms protein-protein interactions with Homer and RTP in the rat vomeronasal organ. BMC Neurosci 11:61

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Miller BA, Cheung JY, Tillotson DL, Hope SM, Scaduto RC Jr (1989) Erythropoietin stimulates a rise in intracellular-free calcium concentration in single BFU-E derived erythroblasts at specific stages of differentiation. Blood 73:1188–1194

    PubMed  CAS  Google Scholar 

  • Misiti J, Spivak JL (1979) Erythropoiesis in vitro. Role of calcium. J Clin Invest 64:1573–1579

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Putney JW (2009) Capacitative calcium entry: from concept to molecules. Immunol Rev 231:10–22

    Article  PubMed  CAS  Google Scholar 

  • Sangokoya C, Telen MJ, Chi JT (2010) microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease. Blood 116:4338–4348

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Spehr J, Hagendorf S, Weiss J, Spehr M, Leinders-Zufall T, Zufall F (2009) Ca2+-calmodulin feedback mediates sensory adaptation and inhibits pheromone-sensitive ion channels in the vomeronasal organ. J Neurosci 29:2125–2135

    Article  PubMed  CAS  Google Scholar 

  • Steinberg MH, Brugnara C (2003) Pathophysiological-based approaches to treatment of sickle cell disease. Annu Rev Med 54:89–112

    Article  PubMed  CAS  Google Scholar 

  • Stowers L, Holy TE, Meister M, Dulac C, Koentges G (2002) Loss of sex discrimination and male-male aggression in mice deficient for TRP2. Science 295:1493–1500

    Article  PubMed  CAS  Google Scholar 

  • Strubing C, Krapivinsky G, Krapivinsky L, Clapham DE (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29:645–655

    Article  PubMed  CAS  Google Scholar 

  • Sukumaran P, Lof C, Kemppainen K, Kankaanpaa P, Pulli I, Nasman J, Viitanen T, Tornquist K (2012) Canonical transient receptor potential channel 2 (TRPC2) as a major regulator of calcium homeostasis in rat thyroid FRTL-5 cells: importance of protein kinase C delta (PKCdelta) and stromal interaction molecule 2 (STIM2). J Biol Chem 287:44345–44360

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Tong Q, Chu X, Cheung JY, Conrad K, Stahl R, Barber DL, Mignery G, Miller BA (2004) Erythropoietin-modulated calcium influx through TRPC2 is mediated by phospholipase Cgamma and IP3R. Am J Physiol Cell Physiol 287:C1667–1678

    Article  PubMed  CAS  Google Scholar 

  • Tong Q, Hirschler-Laszkiewicz I, Zhang W, Conrad K, Neagley DW, Barber DL, Cheung JY, Miller BA (2008) TRPC3 is the erythropoietin-regulated calcium channel in human erythroid cells. J Biol Chem 283:10385–10395

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Vannier B, Peyton M, Boulay G, Brown D, Qin N, Jiang M, Zhu X, Birnbaumer L (1999) Mouse trp2, the homologue of the human trpc2 pseudogene, encodes mTrp2, a store depletion-activated capacitative Ca2+ entry channel. Proc Natl Acad Sci USA 96:2060–2064

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Venkatachalam K, Montell C (2007) TRP channels. Annu Rev Biochem 76:387–417

    Article  PubMed  CAS  Google Scholar 

  • Wes PD, Chevesich J, Jeromin A, Rosenberg C, Stetten G, Montell C (1995) TRPC1, a human homolog of a Drosophila store-operated channel. Proc Natl Acad Sci USA 92:9652–9656

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wissenbach U, Schroth G, Philipp S, Flockerzi V (1998) Structure and mRNA expression of a bovine trp homologue related to mammalian trp2 transcripts. FEBS Lett 429:61–66

    Article  PubMed  CAS  Google Scholar 

  • Xu XZ, Li HS, Guggino WB, Montell C (1997) Coassembly of TRP and TRPL produces a distinct store-operated conductance. Cell 89:1155–1164

    Article  PubMed  CAS  Google Scholar 

  • Xu XZ, Chien F, Butler A, Salkoff L, Montell C (2000) TRPgamma, a drosophila TRP-related subunit, forms a regulated cation channel with TRPL. Neuron 26:647–657

    Article  PubMed  CAS  Google Scholar 

  • Xu XZ, Moebius F, Gill DL, Montell C (2001) Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform. Proc Natl Acad Sci USA 98:10692–10697

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Yildirim E, Birnbaumer L (2007) TRPC2: molecular biology and functional importance. Handb Exp Pharmacol:53–75

    Google Scholar 

  • Yildirim E, Dietrich A, Birnbaumer L (2003) The mouse C-type transient receptor potential 2 (TRPC2) channel: alternative splicing and calmodulin binding to its N terminus. Proc Natl Acad Sci USA 100:2220–2225

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Yu L, Jin W, Wang JX, Zhang X, Chen MM, Zhu ZH, Lee H, Lee M, Zhang YP (2010) Characterization of TRPC2, an essential genetic component of VNS chemoreception, provides insights into the evolution of pheromonal olfaction in secondary-adapted marine mammals. Mol Biol Evol 27:1467–1477

    Article  PubMed  CAS  Google Scholar 

  • Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH, Dehoff MH, Schwarz MK, Seeburg PH, Muallem S et al (2003) Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell 114:777–789

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, Chu X, Tong Q, Cheung JY, Conrad K, Masker K, Miller BA (2003) A novel TRPM2 isoform inhibits calcium influx and susceptibility to cell death. J Biol Chem 278:16222–16229

    Article  PubMed  CAS  Google Scholar 

  • Zhang P, Yang C, Delay RJ (2010) Odors activate dual pathways, a TRPC2 and a AA-dependent pathway, in mouse vomeronasal neurons. Am J Physiol Cell Physiol 298:C1253–1264

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zhao H, Xu D, Zhang S, Zhang J (2011) Widespread losses of vomeronasal signal transduction in bats. Mol Biol Evol 28:7–12

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zhu X, Jiang M, Peyton M, Boulay G, Hurst R, Stefani E, Birnbaumer L (1996) trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Cell 85:661–671

    Article  PubMed  CAS  Google Scholar 

  • Zufall F (2005) The TRPC2 ion channel and pheromone sensing in the accessory olfactory system. Naunyn Schmiedebergs Arch Pharmacol 371:245–250

    Article  PubMed  CAS  Google Scholar 

  • Zufall F, Ukhanov K, Lucas P, Liman ER, Leinders-Zufall T (2005) Neurobiology of TRPC2: from gene to behavior. Pflugers Arch 451:61–71

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Pediatrics and Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA

    Barbara A. Miller

Authors
  1. Barbara A. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Barbara A. Miller .

Editor information

Editors and Affiliations

  1. Laboratory Ion Channel Research Campus Gasthuisberg, KU Leuven Department Cell Mol Medicin, Leuven, Belgium

    Bernd Nilius

  2. Institut für Experimentelle u. Klinische, Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg, Saarland, Germany

    Veit Flockerzi

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Miller, B.A. (2014). TRPC2. In: Nilius, B., Flockerzi, V. (eds) Mammalian Transient Receptor Potential (TRP) Cation Channels. Handbook of Experimental Pharmacology, vol 222. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54215-2_3

Download citation

Publish with us

Policies and ethics

Search

Navigation