Abstract
Store-operated Ca2+ entry (SOCE) is activated in response to depletion of the ER-Ca2+ stores by the ER Ca2+ sensor protein, STIM1 which oligomerizes and moves to ER/PM junctional domains where it interacts with and activates channels involved in SOCE. Two types of channel activities have been described. ICRAC, via Ca2+ release-activated Ca2+ (CRAC) channel, which displays high Ca2+ selectivity and accounts for the SOCE and cell function in T lymphocytes, mast cells, platelets, and some types of smooth muscle and endothelial cells. Orai1 has been established as the pore-forming component of CRAC channels and interaction of Orai1 with STIM1 is sufficient for generation of the CRAC channel. Store depletion also leads to activation of relatively non-selective cation currents (referred to as ISOC) that contribute to SOCE in several other cell types. TRPC channels, including TRPC1, TRPC3, and TRPC4, have been proposed as possible candidate channels for this Ca2+ influx. TRPC1 is the best characterized channel in this regard and reported to contribute to endogenous SOCE in many cells types. TRPC1-mediated Ca2+ entry and cation current in cells stimulated with agonist or thapsigargin are inhibited by low [Gd3+] and 10–20 μM 2APB (conditions that block SOCE). Importantly, STIM1 also associates with and gates TRPC1 via electrostatic interaction between STIM1 (684KK685) and TRPC1 (639DD640). Further, store depletion induces dynamic recruitment of a TRPC1/STIM1/Orai1 complex and knockdown of Orai1 completely abrogates TRPC1 function. Despite these findings, there has been much debate regarding the activation of TRPC1 by store depletion as well as the role of Orai1 and STIM1 in SOC channel function. This chapter summarizes recent studies and concepts regarding the contributions of Orai1 and TRPC1 to SOCE. Major unresolved questions regarding functional interaction between Orai1 and TRPC1 as well as possible mechanisms involved in the regulation of TRPC channels by store depletion will be discussed.
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Parekh AB, Penner R (1997) Store depletion and calcium influx. Physiol Rev 77:901–930
Parekh AB, Putney JW Jr. (2005) Store-operated calcium channels. Physiol Rev 85:757–810
Putney JW Jr. (1990) Capacitative calcium entry revisited. Cell Calcium 11:611–624
Ambudkar IS (2006) Ca2+ signaling microdomains:platforms for the assembly and regulation of TRPC channels. Trends Pharmacol Sci 27:25–32
Putney JW Jr., Broad LM, Braun FJ, Lievremont JP, Bird GS (2001) Mechanisms of capacitative calcium entry. J Cell Sci 114:2223–2229
Bird GS, DeHaven WI, Smyth JT, Putney JW Jr. (2008) Methods for studying store-operated calcium entry. Methods 46:204–212
Prakriya M, Lewis RS (2006) Regulation of CRAC channel activity by recruitment of silent channels to a high open-probability gating mode. J Gen Physiol 128:373–386
Ambudkar IS (2007) TRPC1: a core component of store-operated calcium channels. Biochem Soc Trans 35:96–100
Bolotina VM (2004) Store-operated channels: diversity and activation mechanisms. Sci STKE 2004:pe34
Brueggemann LI, Markun DR, Henderson KK, Cribbs LL, Byron KL (2006) Pharmacological and electrophysiological characterization of store-operated currents and capacitative Ca2+ entry in vascular smooth muscle cells. J Pharmacol Exp Ther 317:488–499
Montell C (2005) The TRP superfamily of cation channels. Sci STKE 2005:re3
Venkatachalam K, Montell C (2007) TRP channels. Annu Rev Biochem 76:387–417
Ambudkar IS, Ong HL, Liu X, Bandyopadhyay BC, Cheng KT (2007) TRPC1: the link between functionally distinct store-operated calcium channels. Cell Calcium 42: 213–223
Venkatachalam K, van Rossum DB, Patterson RL, Ma HT, Gill DL (2002) The cellular and molecular basis of store-operated calcium entry. Nat Cell Biol 4:E263–E272
Beech DJ (2005) Emerging functions of 10 types of TRP cationic channel in vascular smooth muscle. Clin Exp Pharmacol Physiol 32:597–603
Cai S, Fatherazi S, Presland RB, Belton CM, Roberts FA, Goodwin PC, Schubert MM, Izutsu KT (2006) Evidence that TRPC1 contributes to calcium-induced differentiation of human keratinocytes. Pflugers Arch 452:43–52
Dietrich A, Chubanov V, Kalwa H, Rost BR, Gudermann T (2006) Cation channels of the transient receptor potential superfamily: their role in physiological and pathophysiological processes of smooth muscle cells. Pharmacol Ther 112:744–760
Fiorio Pla A, Maric D, Brazer SC, Giacobini P, Liu X, Chang YH, Ambudkar IS, Barker JL (2005) Canonical transient receptor potential 1 plays a role in basic fibroblast growth factor (bFGF)/FGF receptor-1-induced Ca2+ entry and embryonic rat neural stem cell proliferation. J Neurosci 25:2687–2701
Liu X, Cheng KT, Bandyopadhyay BC, Pani B, Dietrich A, Paria BC, Swaim WD, Beech D, Yildrim E, Singh BB, Birnbaumer L, Ambudkar IS (2007) Attenuation of store-operated Ca2+ current impairs salivary gland fluid secretion in TRPC1(–/–) mice. Proc Natl Acad Sci USA 104:17542–17547
Liu X, Wang W, Singh BB, Lockwich T, Jadlowiec J, O’Connell B, Wellner R, Zhu MX, Ambudkar IS (2000) Trp1, a candidate protein for the store-operated Ca2+ influx mechanism in salivary gland cells. J Biol Chem 275:3403–3411
Mehta D, Ahmmed GU, Paria BC, Holinstat M, Voyno-Yasenetskaya T, Tiruppathi C, Minshall RD, Malik AB (2003) RhoA interaction with inositol 1,4,5-trisphosphate receptor and transient receptor potential channel-1 regulates Ca2+ entry. Role in signaling increased endothelial permeability. J Biol Chem 278:33492–33500
Mori Y, Wakamori M, Miyakawa T, Hermosura M, Hara Y, Nishida M, Hirose K, Mizushima A, Kurosaki M, Mori E, Gotoh K, Okada T, Fleig A, Penner R, Iino M, Kurosaki T (2002) Transient receptor potential 1 regulates capacitative Ca2+ entry and Ca2+ release from endoplasmic reticulum in B lymphocytes. J Exp Med 195:673–681
Rao JN, Platoshyn O, Golovina VA, Liu L, Zou T, Marasa BS, Turner DJ, Yuan JX, Wang JY (2006) TRPC1 functions as a store-operated Ca2+ channel in intestinal epithelial cells and regulates early mucosal restitution after wounding. Am J Physiol Gastrointest Liver Physiol 290:G782–G792
Tiruppathi C, Ahmmed GU, Vogel SM, Malik AB (2006) Ca2+ signaling, TRP channels, and endothelial permeability. Microcirculation 13:693–708
Vandebrouck C, Martin D, Colson-Van Schoor M, Debaix H, Gailly P (2002) Involvement of TRPC in the abnormal calcium influx observed in dystrophic (mdx) mouse skeletal muscle fibers. J Cell Biol 158:1089–1096
Zagranichnaya TK, Wu X, Villereal ML (2005) Endogenous TRPC1, TRPC3, and TRPC7 proteins combine to form native store-operated channels in HEK-293 cells. J Biol Chem 280:29559–29569
Dietrich A, Kalwa H, Storch U, Mederos Y, Schnitzler M, Salanova B, Pinkenburg O, Dubrovska G, Essin K, Gollasch M, Birnbaumer L, Gudermann T (2007) Pressure-induced and store-operated cation influx in vascular smooth muscle cells is independent of TRPC1. Pflugers Arch 455:465–477
Varga-Szabo D, Authi KS, Braun A, Bender M, Ambily A, Hassock SR, Gudermann T, Dietrich A, Nieswandt B (2008) Store-operated Ca2+ entry in platelets occurs independently of transient receptor potential (TRP) C1. Pflugers Arch 457:377–387
Freichel M, Vennekens R, Olausson J, Stolz S, Philipp SE, Weissgerber P, Flockerzi V (2005) Functional role of TRPC proteins in native systems: implications from knockout and knock-down studies. J Physiol 567:59–66
Vazquez G, Lievremont JP, St JBG, Putney JW Jr. (2001) Human Trp3 forms both inositol trisphosphate receptor-dependent and receptor-independent store-operated cation channels in DT40 avian B lymphocytes. Proc Natl Acad Sci USA 98:11777–11782
Wang X, Pluznick JL, Wei P, Padanilam BJ, Sansom SC (2004) TRPC4 forms store-operated Ca2+ channels in mouse mesangial cells. Am J Physiol Cell Physiol 287:C357–C364
Freichel M, Suh SH, Pfeifer A, Schweig U, Trost C, Weissgerber P, Biel M, Philipp S, Freise D, Droogmans G, Hofmann F, Flockerzi V, Nilius B (2001) Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4–/– mice. Nat Cell Biol 3:121–127
Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A (2006) A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441:179–185
Prakriya M, Feske S, Gwack Y, Srikanth S, Rao A, Hogan PG (2006) Orai1 is an essential pore subunit of the CRAC channel. Nature 443:230–233
Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Velicelebi G, Stauderman KA (2005) STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol 169: 435–445
Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE Jr., Meyer T (2005) STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol 15:1235–1241
Zhang SL, Yu Y, Roos J, Kozak JA, Deerinck TJ, Ellisman MH, Stauderman KA, Cahalan MD (2005) STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature 437:902–905
Li Z, Lu J, Xu P, Xie X, Chen L, Xu T (2007) Mapping the interacting domains of STIM1 and Orai1 in Ca2+ release-activated Ca2+ channel activation. J Biol Chem 282:29448–29456
Worley PF, Zeng W, Huang GN, Yuan JP, Kim JY, Lee MG, Muallem S (2007) TRPC channels as STIM1-regulated store-operated channels. Cell Calcium 42:205–211
Park CY, Hoover PJ, Mullins FM, Bachhawat P, Covington ED, Raunser S, Walz T, Garcia KC, Dolmetsch RE, Lewis RS (2009) STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell 136:876–890
Heo WD, Inoue T, Park WS, Kim ML, Park BO, Wandless TJ, Meyer T (2006) PI(3,4,5)P3 and PI(4,5)P2 lipids target proteins with polybasic clusters to the plasma membrane. Science 314:1458–1461
Liou J, Fivaz M, Inoue T, Meyer T (2007) Live-cell imaging reveals sequential oligomerization and local plasma membrane targeting of stromal interaction molecule 1 after Ca2+ store depletion. Proc Natl Acad Sci USA 104:9301–9306
Walsh CM, Chvanov M, Haynes LP, Petersen OH, Tepikin AV, Burgoyne RD (2009) Role of phosphoinositides in STIM1 dynamics and store-operated calcium entry. Biochem J 425: 159–168
Korzeniowski MK, Popovic MA, Szentpetery Z, Varnai P, Stojilkovic SS, Balla T (2009) Dependence of STIM1/Orai1-mediated calcium entry on plasma membrane phosphoinositides. J Biol Chem 284:21027–21035
Pani B, Ong HL, Liu X, Rauser K, Ambudkar IS, Singh BB (2008) Lipid rafts determine clustering of STIM1 in endoplasmic reticulum-plasma membrane junctions and regulation of store-operated Ca2+ entry (SOCE). J Biol Chem 283:17333–17340
Alicia S, Angelica Z, Carlos S, Alfonso S, Vaca L (2008) STIM1 converts TRPC1 from a receptor-operated to a store-operated channel: Moving TRPC1 in and out of lipid rafts. Cell Calcium 44:479–491
Jardin I, Salido GM, Rosado JA (2008) Role of lipid rafts in the interaction between hTRPC1, Orai1 and STIM1. Channels (Austin) 2:401–403
DeHaven WI, Jones BF, Petranka JG, Smyth JT, Tomita T, Bird GS, Putney JW Jr. (2009) TRPC channels function independently of STIM1 and Orai1. J Physiol 587:2275–2298
Ambudkar IS, Ong HL, Singh BB (2010) Molecular and functional determinants of Ca2+ signaling microdomains. In: Sitaramayya A (ed) Signal transduction: pathways, mechanisms and diseases. Springer, Heidelberg, pp. 237–253
Pani B, Singh BB (2009) Lipid rafts/caveolae as microdomains of calcium signaling. Cell Calcium 45:625–633
Hogan PG, Lewis RS, Rao A (2010) Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. Annu Rev Immunol 28:491–533
Yeromin AV, Zhang SL, Jiang W, Yu Y, Safrina O, Cahalan MD (2006) Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai. Nature 443:226–229
Luik RM, Wu MM, Buchanan J, Lewis RS (2006) The elementary unit of store-operated Ca2+ entry: local activation of CRAC channels by STIM1 at ER-plasma membrane junctions. J Cell Biol 174:815–825
Xu P, Lu J, Li Z, Yu X, Chen L, Xu T (2006) Aggregation of STIM1 underneath the plasma membrane induces clustering of Orai1. Biochem Biophys Res Commun 350:969–976
Prakriya M (2009) The molecular physiology of CRAC channels. Immunol Rev 231:88–98
Kawasaki T, Lange I, Feske S (2009) A minimal regulatory domain in the C terminus of STIM1 binds to and activates ORAI1 CRAC channels. Biochem Biophys Res Commun 385:49–54
Muik M, Fahrner M, Derler I, Schindl R, Bergsmann J, Frischauf I, Groschner K, Romanin C (2009) A cytosolic homomerization and a modulatory domain within STIM1 C terminus determine coupling to ORAI1 channels. J Biol Chem 284:8421–8426
Yuan JP, Zeng W, Dorwart MR, Choi YJ, Worley PF, Muallem S (2009) SOAR and the polybasic STIM1 domains gate and regulate Orai channels. Nat Cell Biol 11:337–343
Mullins FM, Park CY, Dolmetsch RE, Lewis RS (2009) STIM1 and calmodulin interact with Orai1 to induce Ca2+-dependent inactivation of CRAC channels. Proc Natl Acad Sci USA 106:15495–15500
Cheng KT, Liu X, Ong HL, Ambudkar IS (2008) Functional requirement for Orai1 in store-operated TRPC1-STIM1 channels. J Biol Chem 283:12935–12940
Huang GN, Zeng W, Kim JY, Yuan JP, Han L, Muallem S, Worley PF (2006) STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels. Nat Cell Biol 8:1003–1010
Ong HL, Cheng KT, Liu X, Bandyopadhyay BC, Paria BC, Soboloff J, Pani B, Gwack Y, Srikanth S, Singh BB, Gill DL, Ambudkar IS (2007) Dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in store-operated calcium influx. Evidence for similarities in store-operated and calcium release-activated calcium channel components. J Biol Chem 282:9105–9116
Lopez JJ, Salido GM, Pariente JA, Rosado JA (2006) Interaction of STIM1 with endogenously expressed human canonical TRP1 upon depletion of intracellular Ca2+ stores. J Biol Chem 281:28254–28264
Yuan JP, Zeng W, Huang GN, Worley PF, Muallem S (2007) STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels. Nat Cell Biol 9:636–645
Zeng W, Yuan JP, Kim MS, Choi YJ, Huang GN, Worley PF, Muallem S (2008) STIM1 gates TRPC channels, but not Orai1, by electrostatic interaction. Mol Cell 32:439–448
Kim MS, Zeng W, Yuan JP, Shin DM, Worley PF, Muallem S (2009) Native store-operated Ca2+ influx requires the channel function of orai1 and TRPC1. J Biol Chem 284:9733–9741
Jardin I, Lopez JJ, Salido GM, Rosado JA (2008) Orai1 mediates the interaction between STIM1 and hTRPC1 and regulates the mode of activation of hTRPC1-forming Ca2+ channels. J Biol Chem 283:25296–25304
Liao Y, Erxleben C, Yildirim E, Abramowitz J, Armstrong DL, Birnbaumer L (2007) Orai proteins interact with TRPC channels and confer responsiveness to store depletion. Proc Natl Acad Sci USA 104:4682–4687
Liu X, Groschner K, Ambudkar IS (2004) Distinct Ca2+-permeable cation currents are activated by internal Ca2+-store depletion in RBL-2H3 cells and human salivary gland cells, HSG and HSY. J Membr Biol 200:93–104
Liu X, Bandyopadhyay BC, Singh BB, Groschner K, Ambudkar IS (2005) Molecular analysis of a store-operated and 2-acetyl-sn-glycerol-sensitive non-selective cation channel. Heteromeric assembly of TRPC1-TRPC3. J Biol Chem 280:21600–21606
Bair AM, Thippegowda PB, Freichel M, Cheng N, Ye RD, Vogel SM, Yu Y, Flockerzi V, Malik AB, Tiruppathi C (2009) Ca2+ entry via TRPC channels is necessary for thrombin-induced NF-kappaB activation in endothelial cells through AMP-activated protein kinase and protein kinase Cdelta. J Biol Chem 284:563–574
Ohba T, Watanabe H, Takahashi Y, Suzuki T, Miyoshi I, Nakayama S, Satoh E, Iino K, Sasano H, Mori Y, Kuromitsu S, Imagawa K, Saito Y, Iijima T, Ito H, Murakami M (2006) Regulatory role of neuron-restrictive silencing factor in expression of TRPC1. Biochem Biophys Res Commun 351:764–770
Seth M, Zhang ZS, Mao L, Graham V, Burch J, Stiber J, Tsiokas L, Winn M, Abramowitz J, Rockman HA, Birnbaumer L, Rosenberg P (2009) TRPC1 channels are critical for hypertrophic signaling in the heart. Circ Res 105:1023–1030
Scharenberg AM, Humphries LA, Rawlings DJ (2007) Calcium signalling and cell-fate choice in B cells. Nat Rev Immunol 7:778–789
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Cheng, K.T., Ong, H.L., Liu, X., Ambudkar, I.S. (2011). Contribution of TRPC1 and Orai1 to Ca2+ Entry Activated by Store Depletion. In: Islam, M. (eds) Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology, vol 704. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0265-3_24
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