Skip to main content
SpringerLink
Log in

Role of Scaffolding Proteins in the Regulation of TRPC-Dependent Calcium Entry

  • Chapter
  • First Online:
Calcium Entry Pathways in Non-excitable Cells

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 898))

Abstract

Plasma membrane ion channels, and in particular TRPC channels need a specific membrane environment and association with scaffolding, signaling, and cytoskeleton proteins in order to play their important functional role. The molecular composition of TRPC channels is an important factor in determining channel activation mechanisms. TRPC proteins are incorporated in macromolecular complexes including several key Ca2 + signaling proteins as well as proteins involved in vesicle trafficking, cytoskeletal interactions, and scaffolding. Evidence has been provided for association of TRPC with calmodulin (CaM), IP3R, PMCA, Gq/11, RhoA, and a variety of scaffolding proteins. The interaction between TRPC channels with adaptor proteins, determines their mode of regulation as well as their cellular localization and function. Adaptor proteins do not display any enzymatic activity but act as scaffold for the building of signaling complexes. The scaffolding proteins are involved in the assembling of these Ca2+ signaling complexes, the correct sub-cellular localization of protein partners, and the regulation of the TRPC channelosome. In particular, these proteins, via their multiple protein–protein interaction motifs, can interact with various ion channels involved in the transmembrane potential, and membrane excitability. Scaffolding proteins are key components for the functional organization of TRPC channelosomes that serves as a platform regulating slow Ca2+ entry, spatially and temporally controlled [Ca2+]i signals and Ca2+ -dependent cellular functions.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • 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

References

  1. Harris BZ, Lim WA (2001) Mechanism and role of PDZ domains in signaling complex assembly. J Cell Sci 114:3219–3231

    CAS  PubMed  Google Scholar 

  2. Garbett D, Bretscher A (2014) The surprising dynamics of scaffolding proteins. Mol Biol Cell 25(16):2315–2319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Walther C, Ferguson SS (2015) Minireview: role of intracellular scaffolding proteins in the regulation of endocrine g protein-coupled receptor signaling. Mol Endocrinol 29(6):814–830

    Article  CAS  PubMed  Google Scholar 

  4. Catterall WA (2011) Voltage-gated calcium channels. Cold Spring Harb Perspect Biol 3(8):a003947

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Roderick HL, Cook SJ (2008) Ca2+ signalling checkpoints in cancer: remodelling Ca2+ for cancer cell proliferation and survival. Nat Rev Cancer 8(5):361–375

    Article  CAS  PubMed  Google Scholar 

  6. Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4(7):517–529

    Article  CAS  PubMed  Google Scholar 

  7. Benemei S, Patacchini R, Trevisani M, Geppetti P (2015) TRP channels. Curr Opin Pharmacol 22:18–23

    Article  CAS  PubMed  Google Scholar 

  8. Hellmich UA, Gaudet R (2014) Structural biology of TRP channels. Handb Exp Pharmacol 223:963–990

    Article  CAS  PubMed  Google Scholar 

  9. Montell C (2011) The history of TRP channels, a commentary and reflection. Pflugers Arch 461(5):499–506

    Article  CAS  PubMed  Google Scholar 

  10. Zheng J (2013) Molecular mechanism of TRP channels. Compr Physiol 3(1):221–242

    PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Montell C (2012) Drosophila visual transduction. Trends Neurosci 35(6):356–363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hardie RC, Juusola M (2015) Phototransduction in Drosophila. Curr Opin Neurobiol 34C:37–45

    Article  CAS  Google Scholar 

  14. Shieh BH, Zhu MY (1996) Regulation of the TRP Ca2+ channel by INAD in Drosophila photoreceptors. Neuron 16(5):991–998

    Article  CAS  PubMed  Google Scholar 

  15. Huber A, Sander P, Bähner M, Paulsen R (1998) The TRP Ca2+ channel assembled in a signaling complex by the PDZ domain protein INAD is phosphorylated through the interaction with protein kinase C (ePKC). FEBS Lett 425(2):317–322

    Article  CAS  PubMed  Google Scholar 

  16. Xu XZ, Choudhury A, Li X, Montell C (1998) Coordination of an array of signaling proteins through homo- and heteromeric interactions between PDZ domains and target proteins. J Cell Biol 142(2):545–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chevesich J, Kreuz AJ, Montell C (1997) Requirement for the PDZ domain protein, INAD, for localization of the TRP store-operated channel to a signaling complex. Neuron 18(1):95–105

    Article  CAS  PubMed  Google Scholar 

  18. Wes PD, Xu XZ, Li HS, Chien F, Doberstein SK, Montell C (1999) Termination of phototransduction requires binding of the NINAC myosin III and the PDZ protein INAD. Nat Neurosci 2(5):447–453

    Article  CAS  PubMed  Google Scholar 

  19. Tsunoda S, Sierralta J, Sun Y, Bodner R, Suzuki E, Becker A, Socolich M, Zuker CS (1997) A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade. Nature 388(6639):243–249

    Article  CAS  PubMed  Google Scholar 

  20. Li HS, Montell C (2000) TRP and the PDZ protein, INAD, form the core complex required for retention of the signalplex in Drosophila photoreceptor cells. J Cell Biol 150(6):1411–1422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bähner M, Frechter S, Da Silva N, Minke B, Paulsen R, Huber A (2002) Light-regulated subcellular translocation of Drosophila TRPL channels induces long-term adaptation and modifies the light-induced current. Neuron 34(1):83–93

    Article  PubMed  Google Scholar 

  22. Goel M, Sinkins WG, Schilling WP (2002) Selective association of TRPC channel subunits in rat brain synaptosomes. J Biol Chem 277(50):48303–48310

    Article  CAS  PubMed  Google Scholar 

  23. 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 U S A 92(21):9652–9656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Owsianik G, Talavera K, Voets T, Nilius B (2006) Permeation and selectivity of TRP channels. Annu Rev Physiol 68:685–717

    Article  CAS  PubMed  Google Scholar 

  25. Parekh AB, Putney JW Jr (2005) Store-operated calcium channels. Physiol Rev 85(2):757–810

    Article  CAS  PubMed  Google Scholar 

  26. Cheng KT, Ong HL, Liu X, Ambudkar IS (2013) Contribution and regulation of TRPC channels in store-operated Ca2+ entry. Curr Top Membr 71:149–179

    Article  CAS  PubMed  Google Scholar 

  27. Xu SZ, Beech DJ (2001) TrpC1 is a membrane-spanning subunit of store-operated Ca2+ channels in native vascular smooth muscle cells. Circ Res 88(1):84–87

    Article  CAS  PubMed  Google Scholar 

  28. Chen J, Crossland RF, Noorani MM, Marrelli SP (2009) Inhibition of TRPC1/TRPC3 by PKG contributes to NO-mediated vasorelaxation. Am J Physiol Heart Circ Physiol 297(1):H417–H424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Xu SZ, Boulay G, Flemming R, Beech DJ (2006) E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles. Am J Physiol Heart Circ Physiol 291(6):H2653–H2659

    Article  CAS  PubMed  Google Scholar 

  30. Saleh SN, Albert AP, Peppiatt-Wildman CM, Large WA (2008) Diverse properties of store-operated TRPC channels activated by protein kinase C in vascular myocytes. J Physiol 586(10):2463–2476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Philipp S, Trost C, Warnat J, Rautmann J, Himmerkus N, Schroth G, Kretz O, Nastainczyk W, Cavalie A, Hoth M, Flockerzi V (2000) TRP4 (CCE1) protein is part of native calcium release-activated Ca2 +-like channels in adrenal cells. J Biol Chem 275(31):23965–23972

    Article  CAS  PubMed  Google Scholar 

  32. Yang H, Mergler S, Sun X, Wang Z, Lu L, Bonanno JA, Pleyer U, Reinach PS (2005) TRPC4 knockdown suppresses epidermal growth factor-induced store-operated channel activation and growth in human corneal epithelial cells. J Biol Chem 280(37):32230–32237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bréchard S, Melchior C, Plançon S, Schenten V, Tschirhart EJ (2008) Store-operated Ca2+ channels formed by TRPC1, TRPC6 and Orai1 and non-store-operated channels formed by TRPC3 are involved in the regulation of NADPH oxidase in HL-60 granulocytes. Cell Calcium 44(5):492–506

    Article  PubMed  CAS  Google Scholar 

  34. 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(5):3403–3411

    Article  CAS  PubMed  Google Scholar 

  35. 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(6):673–681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 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(6):1089–1096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 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(35):33492–33500

    Article  CAS  PubMed  Google Scholar 

  38. 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(10):2687–2701

    Article  PubMed  CAS  Google Scholar 

  39. 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(1):43–52

    Article  CAS  PubMed  Google Scholar 

  40. 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(4):G782–G792

    Article  CAS  PubMed  Google Scholar 

  41. 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(22):21600–21606

    Article  CAS  PubMed  Google Scholar 

  42. Wu X, Zagranichnaya TK, Gurda GT, Eves EM, Villereal ML (2004) A TRPC1/TRPC3-mediated increase in store-operated calcium entry is required for differentiation of H19-7 hippocampal neuronal cells. J Biol Chem 279(42):43392–43402

    Article  CAS  PubMed  Google Scholar 

  43. Shi J, Ju M, Saleh SN, Albert AP, Large WA (2010) TRPC6 channels stimulated by angiotensin II are inhibited by TRPC1/C5 channel activity through a Ca2+- and PKC-dependent mechanism in native vascular myocytes. J Physiol 588(Pt 19):3671–3682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Shi J, Ju M, Abramowitz J, Large WA, Birnbaumer L, Albert AP (2012) TRPC1 proteins confer PKC and phosphoinositol activation on native heteromeric TRPC1/C5 channels in vascular smooth muscle: comparative study of wild-type and TRPC1-/- mice. FASEB J 26(1):409–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tsvilovskyy VV, Zholos AV, Aberle T, Philipp SE, Dietrich A, Zhu MX, Birnbaumer L, Freichel M, Flockerzi V (2009) Deletion of TRPC4 and TRPC6 in mice impairs smooth muscle contraction and intestinal motility in vivo. Gastroenterology 137(4):1415–1424

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Sundivakkam PC, Freichel M, Singh V, Yuan JP, Vogel SM, Flockerzi V, Malik AB, Tiruppathi C (2012) The Ca2+ sensor stromal interaction molecule 1 (STIM1) is necessary and sufficient for the store-operated Ca(2+) entry function of transient receptor potential canonical (TRPC) 1 and 4 channels in endothelial cells. Mol Pharmacol 81(4):510–526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Sabourin J, Lamiche C, Vandebrouck A, Magaud C, Rivet J, Cognard C, Bourmeyster N, Constantin B (2009) Regulation of TRPC1 and TRPC4 cation channels requires an alpha1-syntrophin-dependent complex in skeletal mouse myotubes. J Biol Chem 284(52):36248–36261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. 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(33):29559–29569

    Article  CAS  PubMed  Google Scholar 

  49. 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 U S A 104(44):17542–17547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sun Y, Birnbaumer L, Singh BB (2015) TRPC1 regulates calcium-activated chloride channels in salivary gland cells. J Cell Physiol 230(11):2848–2856

    Article  CAS  PubMed  Google Scholar 

  51. Kim MS, Hong JH, Li Q, Shin DM, Abramowitz J, Birnbaumer L, Muallem S (2009) Deletion of TRPC3 in mice reduces store-operated Ca2+ influx and the severity of acute pancreatitis. Gastroenterology 137(4):1509–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. 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(2):121–127

    Article  CAS  PubMed  Google Scholar 

  53. Tiruppathi C, Freichel M, Vogel SM, Paria BC, Mehta D, Flockerzi V, Malik AB (2002) Impairment of store-operated Ca2+ entry in TRPC4(-/-) mice interferes with increase in lung microvascular permeability. Circ Res 91(1):70–76

    Article  CAS  PubMed  Google Scholar 

  54. Medic N, Desai A, Olivera A, Abramowitz J, Birnbaumer L, Beaven MA, Gilfillan AM, Metcalfe DD (2013) Knockout of the Trpc1 gene reveals that TRPC1 can promote recovery from anaphylaxis by negatively regulating mast cell TNF-α production. Cell Calcium 53(5–6):315–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lee KP, Jun JY, Chang IY, Suh SH, So I, Kim KW (2005) TRPC4 is an essential component of the nonselective cation channel activated by muscarinic stimulation in mouse visceral smooth muscle cells. Mol Cells 20(3):435–441

    CAS  PubMed  Google Scholar 

  56. Camacho Londoño JE, Tian Q, Hammer K, Schröder L, Camacho Londoño J, Reil JC, He T, Oberhofer M, Mannebach S, Mathar I, Philipp SE, Tabellion W, Schweda F, Dietrich A, Kaestner L, Laufs U, Birnbaumer L, Flockerzi V, Freichel M, Lipp P (2015) A background Ca2+ entry pathway mediated by TRPC1/TRPC4 is critical for development of pathological cardiac remodelling. Eur Heart J. doi:10.1093/eurheartj/ehv250

    PubMed  Google Scholar 

  57. Hogan PG, Rao A (2015) Store-operated calcium entry: mechanisms and modulation. Biochem Biophys Res Commun 460(1):40–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hogan PG (2015) The STIM1-ORAI1 microdomain. Cell Calcium 58(6):357–367, pii: S0143-4160(15)00117-7

    Article  CAS  PubMed  Google Scholar 

  59. 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(13):1235–1241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Veliçelebi G, Stauderman KA (2005) STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol 169(3):435–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 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(3):337–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. 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(13):8421–8426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Schindl R, Muik M, Fahrner M, Derler I, Fritsch R, Bergsmann J, Romanin C (2009) Recent progress on STIM1 domains controlling Orai activation. Cell Calcium 46(4):227–232

    Article  CAS  PubMed  Google Scholar 

  64. Korzeniowski MK, Manjarrés IM, Varnai P, Balla T (2010) Activation of STIM1-Orai1 involves an intramolecular switching mechanism. Sci Signal 3(148):ra82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. 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(9):1003–1010

    Article  CAS  PubMed  Google Scholar 

  66. Yuan JP, Kim MS, Zeng W, Shin DM, Huang G, Worley PF, Muallem S (2009) TRPC channels as STIM1-regulated SOCs. Channels (Austin) 3(4):221–225

    Article  CAS  Google Scholar 

  67. 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(6):636–645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. 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(12):9105–9116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Liao Y, Erxleben C, Abramowitz J, Flockerzi V, Zhu MX, Armstrong DL, Birnbaumer L (2008) Functional interactions among Orai1, TRPCs, and STIM1 suggest a STIM-regulated heteromeric Orai/TRPC model for SOCE/Icrac channels. Proc Natl Acad Sci U S A 105(8):2895–2900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Liao Y, Plummer NW, George MD, Abramowitz J, Zhu MX, Birnbaumer L (2009) A role for Orai in TRPC-mediated Ca2+ entry suggests that a TRPC:Orai complex may mediate store and receptor operated Ca2+ entry. Proc Natl Acad Sci U S A 106(9):3202–3206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. 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(15):9733–9741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Cheng KT, Liu X, Ong HL, Swaim W, Ambudkar IS (2011) Local Ca2+ entry via Orai1 regulates plasma membrane recruitment of TRPC1 and controls cytosolic Ca2+ signals required for specific cell functions. PLoS Biol 9(3):e1001025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ong HL, Ambudkar IS (2015) Molecular determinants of TRPC1 regulation within ER-PM junctions. Cell Calcium. doi:10.1016/j.ceca.2015.03.008

    PubMed  Google Scholar 

  74. Sabourin J, Harisseh R, Harnois T, Magaud C, Bourmeyster N, Déliot N, Constantin B (2012) Dystrophin/α1-syntrophin scaffold regulated PLC/PKC-dependent store-operated calcium entry in myotubes. Cell Calcium 2012(6):445–456

    Article  CAS  Google Scholar 

  75. Antigny F, Koenig S, Bernheim L, Frieden M (2013) During post-natal human myogenesis, normal myotube size requires TRPC1- and TRPC4-mediated Ca2+ entry. J Cell Sci 126(Pt 11):2525–2533

    Article  CAS  PubMed  Google Scholar 

  76. Smani T, Dionisio N, López JJ, Berna-Erro A, Rosado JA (2014) Cytoskeletal and scaffolding proteins as structural and functional determinants of TRP channels. Biochim Biophys Acta 1838(2):658–664

    Article  CAS  PubMed  Google Scholar 

  77. Ambudkar IS, Ong HL (2007) Organization and function of TRPC channelosomes. Pflugers Arch 455(2):187–200

    Article  CAS  PubMed  Google Scholar 

  78. Fridolfsson HN, Roth DM, Insel PA, Patel HH (2014) Regulation of intracellular signaling and function by caveolin. FASEB J 28(9):3823–3831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Brazer SC, Singh BB, Liu X, Swaim W, Ambudkar IS (2003) Caveolin-1 contributes to assembly of store-operated Ca2+ influx channels by regulating plasma membrane localization of TRPC1. J Biol Chem 278(29):27208–27215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kwiatek AM, Minshall RD, Cool DR, Skidgel RA, Malik AB, Tiruppathi C (2006) Caveolin-1 regulates store-operated Ca2+ influx by binding of its scaffolding domain to transient receptor potential channel-1 in endothelial cells. Mol Pharmacol 70(4):1174–1183

    Article  CAS  PubMed  Google Scholar 

  81. Sundivakkam PC, Kwiatek AM, Sharma TT, Minshall RD, Malik AB, Tiruppathi C (2009) Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells. Am J Physiol Cell Physiol 296(3):C403–C413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Murata T, Lin MI, Stan RV, Bauer PM, Yu J, Sessa WC (2007) Genetic evidence supporting caveolae microdomain regulation of calcium entry in endothelial cells. J Biol Chem 282(22):16631–16643

    Article  CAS  PubMed  Google Scholar 

  83. Lockwich TP, Liu X, Singh BB, Jadlowiec J, Weiland S, Ambudkar IS (2000) Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains. J Biol Chem 275(16):11934–11942

    Article  CAS  PubMed  Google Scholar 

  84. Pani B, Ong HL, Brazer SC, Liu X, Rauser K, Singh BB, Ambudkar IS (2009) Activation of TRPC1 by STIM1 in ER-PM microdomains involves release of the channel from its scaffold caveolin-1. Proc Natl Acad Sci U S A 106(47):20087–20092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Pani B, Liu X, Bollimuntha S, Cheng KT, Niesman IR, Zheng C, Achen VR, Patel HH, Ambudkar IS, Singh BB (2012) Impairment of TRPC1-STIM1 channel assembly and AQP5 translocation compromise agonist-stimulated fluid secretion in mice lacking caveolin1. J Cell Sci 126(Pt 2):667–675

    PubMed  Google Scholar 

  86. Ingueneau C, Huynh UD, Marcheix B, Athias A, Gambert P, Nègre-Salvayre A, Salvayre R, Vindis C (2009) TRPC1 is regulated by caveolin-1 and is involved in oxidized LDL-induced apoptosis of vascular smooth muscle cells. J Cell Mol Med 13(8B):1620–1631

    Article  PubMed  Google Scholar 

  87. Huang YW, Chang SJ, I-Chen Harn H, Huang HT, Lin HH, Shen MR, Tang MJ, Chiu WT (2015) Mechanosensitive store-operated calcium entry regulates the formation of cell polarity. J Cell Physiol 230(9):2086–2097

    Article  CAS  PubMed  Google Scholar 

  88. Lockwich T, Singh BB, Liu X, Ambudkar IS (2001) Stabilization of cortical actin induces internalization of transient receptor potential 3 (Trp3)-associated caveolar Ca2+ signaling complex and loss of Ca2+ influx without disruption of Trp3-inositol trisphosphate receptor association. J Biol Chem 276(45):42401–42408

    Article  CAS  PubMed  Google Scholar 

  89. Adebiyi A, Narayanan D, Jaggar JH (2011) Caveolin-1 assembles type 1 inositol 1,4,5-trisphosphate receptors and canonical transient receptor potential 3 channels into a functional signaling complex in arterial smooth muscle cells. J Biol Chem 286(6):4341–4348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Misra UK, Mowery YM, Gawdi G, Pizzo SV (2011) Loss of cell surface TFII-I promotes apoptosis in prostate cancer cells stimulated with activated α2-macroglobulin. J Cell Biochem 112(6):1685–1695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Eder P, Probst D, Rosker C, Poteser M, Wolinski H, Kohlwein SD, Romanin C, Groschner K (2007) Phospholipase C-dependent control of cardiac calcium homeostasis involves a TRPC3-NCX1 signaling complex. Cardiovasc Res 73(1):111–119

    Article  CAS  PubMed  Google Scholar 

  92. Gervásio OL, Whitehead NP, Yeung EW, Phillips WD, Allen DG (2008) TRPC1 binds to caveolin-3 and is regulated by Src kinase – role in Duchenne muscular dystrophy. J Cell Sci 121(Pt 13):2246–2255

    Article  PubMed  CAS  Google Scholar 

  93. Sabourin J, Cognard C, Constantin B (2009) Regulation by scaffolding proteins of canonical transient receptor potential channels in striated muscle. J Muscle Res Cell Motil 30(7–8):289–297

    Article  CAS  PubMed  Google Scholar 

  94. Stiber JA, Zhang ZS, Burch J, Eu JP, Zhang S, Truskey GA, Seth M, Yamaguchi N, Meissner G, Shah R, Worley PF, Williams RS, Rosenberg PB (2008) Mice lacking Homer 1 exhibit a skeletal myopathy characterized by abnormal transient receptor potential channel activity. Mol Cell Biol 28(8):2637–2647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Vandebrouck A, Sabourin J, Rivet J, Balghi H, Sebille S, Kitzis A, Raymond G, Cognard C, Bourmeyster N, Constantin B (2007) Regulation of capacitative calcium entries by alpha1-syntrophin: association of TRPC1 with dystrophin complex and the PDZ domain of alpha1-syntrophin. FASEB J 21(2):608–617

    Article  CAS  PubMed  Google Scholar 

  96. Bhat HF, Adams ME, Khanday FA (2013) Syntrophin proteins as Santa Claus: role(s) in cell signal transduction. Cell Mol Life Sci 70(14):2533–2554

    Article  CAS  PubMed  Google Scholar 

  97. Constantin B (2014) Dystrophin complex functions as a scaffold for signalling proteins. Biochim Biophys Acta 1838(2):635–642

    Article  CAS  PubMed  Google Scholar 

  98. Adams ME, Butler MH, Dwyer TM, Peters MF, Murnane AA, Froehner SC (1993) Two forms of mouse syntrophin, a 58 kd dystrophin-associated protein, differ in primary structure and tissue distribution. Neuron 11:531–540

    Article  CAS  PubMed  Google Scholar 

  99. Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC (1998) Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins. J Neurosci 18:128–137

    CAS  PubMed  Google Scholar 

  100. Gavillet B, Rougier JS, Domenighetti AA, Behar R, Boixel C, Ruchat P, Lehr HA, Pedrazzini T, Abriel H (2006) Cardiac sodium channel Nav1.5 is regulated by a multiprotein complex composed of syntrophins and dystrophin. Circ Res 99(4):407–414

    Article  CAS  PubMed  Google Scholar 

  101. Shy D, Gillet L, Ogrodnik J, Albesa M, Verkerk AO, Wolswinkel R, Rougier JS, Barc J, Essers MC, Syam N, Marsman RF, van Mil AM, Rotman S, Redon R, Bezzina CR, Remme CA, Abriel H (2014) PDZ domain-binding motif regulates cardiomyocyte compartment-specific NaV1.5 channel expression and function. Circulation 130(2):147–160

    Article  CAS  PubMed  Google Scholar 

  102. Connors NC, Adams ME, Froehner SC, Kofuji P (2004) The potassium channel Kir4.1 associates with the dystrophin-glycoprotein complex via alpha-syntrophin in glia. J Biol Chem 279:28387–28392

    Article  CAS  PubMed  Google Scholar 

  103. Harisseh R, Chatelier A, Magaud C, Déliot N, Constantin B (2013) Involvement of TRPV2 and SOCE in calcium influx disorder in DMD primary human myotubes with a specific contribution of α1-syntrophin and PLC/PKC in SOCE regulation. Am J Physiol Cell Physiol 304(9):C881–C894

    Article  CAS  PubMed  Google Scholar 

  104. Xiao B, Tu JC, Petralia RS, Yuan JP, Doan A, Breder CD, Ruggiero A, Lanahan AA, Wenthold RJ, Worley PF (1998) Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins. Neuron 21(4):707–716

    Article  CAS  PubMed  Google Scholar 

  105. Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH, Dehoff MH, Schwarz MK, Seeburg PH, Muallem S, Worley PF (2003) Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell 114(6):777–789

    Article  CAS  PubMed  Google Scholar 

  106. Beneken J, Tu JC, Xiao B, Nuriya M, Yuan JP, Worley PF, Leahy DJ (2000) Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition. Neuron 26(1):143–154

    Article  CAS  PubMed  Google Scholar 

  107. Hayashi MK, Ames HM, Hayashi Y (2006) Tetrameric hub structure of postsynaptic scaffolding protein homer. J Neurosci 26(33):8492–8501

    Article  CAS  PubMed  Google Scholar 

  108. Worley PF, Zeng W, Huang G, Kim JY, Shin DM, Kim MS, Yuan JP, Kiselyov K, Muallem S (2007) Homer proteins in Ca2+ signaling by excitable and non-excitable cells. Cell Calcium 42(4–5):363–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Salanova M, Volpe P, Blottner D (2013) Homer protein family regulation in skeletal muscle and neuromuscular adaptation. IUBMB Life 65(9):769–776

    Article  CAS  PubMed  Google Scholar 

  110. Jardin I, López JJ, Berna-Erro A, Salido GM, Rosado JA (2013) Homer proteins in Ca2+ entry. IUBMB Life 65(6):497–504

    Article  CAS  PubMed  Google Scholar 

  111. Kim JY, Zeng W, Kiselyov K, Yuan JP, Dehoff MH, Mikoshiba K, Worley PF, Muallem S (2006) Homer 1 mediates store- and inositol 1,4,5-trisphosphate receptor-dependent translocation and retrieval of TRPC3 to the plasma membrane. J Biol Chem 281(43):32540–32549

    Article  CAS  PubMed  Google Scholar 

  112. Lee KP, Yuan JP, So I, Worley PF, Muallem S (2010) STIM1-dependent and STIM1-independent function of transient receptor potential canonical (TRPC) channels tunes their store-operated mode. J Biol Chem 285(49):38666–38673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. 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(3):439–448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Yuan JP, Lee KP, Hong JH, Muallem S (2012) The closing and opening of TRPC channels by Homer1 and STIM1. Acta Physiol (Oxf) 204(2):238–247

    Article  CAS  Google Scholar 

  115. Jardin I, Albarrán L, Bermejo N, Salido GM, Rosado JA (2012) Homers regulate calcium entry and aggregation in human platelets: a role for Homers in the association between STIM1 and Orai1. Biochem J 445(1):29–38

    Article  CAS  PubMed  Google Scholar 

  116. Yun CH, Oh S, Zizak M, Steplock D, Tsao S, Tse CM, Weinman EJ, Donowitz M (1997) cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein. Proc Natl Acad Sci U S A 94(7):3010–3015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Murthy A, Gonzalez-Agosti C, Cordero E, Pinney D, Candia C, Solomon F, Gusella J, Ramesh V (1998) NHE-RF, a regulatory cofactor for Na+-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins. J Biol Chem 273(3):1273–1276

    Article  CAS  PubMed  Google Scholar 

  118. Yun CH, Lamprecht G, Forster DV, Sidor A (1998) NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin. J Biol Chem 273(40):25856–25863

    Article  CAS  PubMed  Google Scholar 

  119. Terawaki S, Maesaki R, Hakoshima T (2006) Structural basis for NHERF recognition by ERM. Structure 14(4):777–789

    Article  CAS  PubMed  Google Scholar 

  120. Ardura JA, Friedman PA (2011) Regulation of G protein-coupled receptor function by Na+/H+ exchange regulatory factors. Pharmacol Rev 63(4):882–900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Dunn HA, Ferguson SS (2015) PDZ protein regulation of GPCR trafficking and signaling pathways. Mol Pharmacol 88:624–639, pii: mol.115.098509

    Article  CAS  PubMed  Google Scholar 

  122. Reczek D, Berryman M, Bretscher A (1997) Identification of EBP50: a PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family. J Cell Biol 139(1):169–179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Tang Y, Tang J, Chen Z, Trost C, Flockerzi V, Li M, Ramesh V, Zhu MX (2000) Association of mammalian trp4 and phospholipase C isozymes with a PDZ domain-containing protein. NHERF J Biol Chem 275(48):37559–37564

    Article  CAS  PubMed  Google Scholar 

  124. Suh PG, Hwang JI, Ryu SH, Donowitz M, Kim JH (2001) The roles of PDZ-containing proteins in PLC-beta-mediated signaling. Biochem Biophys Res Commun 288(1):1–7

    Article  CAS  PubMed  Google Scholar 

  125. Mery L, Strauss B, Dufour JF, Krause KH, Hoth M (2002) The PDZ-interacting domain of TRPC4 controls its localization and surface expression in HEK293 cells. J Cell Sci 115(Pt 17):3497–3508

    CAS  PubMed  Google Scholar 

  126. Lee-Kwon W, Wade JB, Zhang Z, Pallone TL, Weinman EJ (2005) Expression of TRPC4 channel protein that interacts with NHERF. Am J Physiol Cell Physiol 288(4):C942–C949

    Article  CAS  PubMed  Google Scholar 

  127. Obukhov AG, Nowycky MC (2004) TRPC5 activation kinetics are modulated by the scaffolding protein ezrin/radixin/moesin-binding phosphoprotein-50 (EBP50). J Cell Physiol 201(2):227–235

    Article  CAS  PubMed  Google Scholar 

  128. Hoffman T, Schaefer M, Schultz G, Gudermann T (2002) Subunit composition of mammalian ransient receptor potential channels in living cells. Proc Natl Acad Sci U S A 99:7461–7466

    Article  CAS  Google Scholar 

  129. Abramowitz J, Birnbaumer L (2009) Physiology and pathophysiology of canonical transient receptor potential channels. FASEB J 23(2):297–328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Ong HL, de Souza LB, Cheng KT, Ambudkar IS (2014) Physiological functions and regulation of TRPC channels. Handb Exp Pharmacol 223:1005–1034

    Article  CAS  PubMed  Google Scholar 

  131. Tian D, Jacobo SM, Billing D, Rozkalne A, Gage SD, Anagnostou T, Pavenstädt H, Hsu HH, Schlondorff J, Ramos A, Greka A (2010) Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels. Sci Signal 3(145):ra77

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Kerstein PC, Jacques-Fricke BT, Rengifo J, Mogen BJ, Williams JC, Gottlieb PA, Sachs F, Gomez TM (2013) Mechanosensitive TRPC1 channels promote calpain proteolysis of talin to regulate spinal axon outgrowth. J Neurosci 33(1):273–285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory STIM, ERL-7368 CNRS-Université de Poitiers, 1, rue Georges Bonnet, Bat. B36, Pôle Biologie-Santé, 86000, Poitiers, France

    Bruno Constantin

Authors
  1. Bruno Constantin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bruno Constantin .

Editor information

Editors and Affiliations

  1. Depto. Fisiología, University of Extremadura, Cáceres, Spain

    Juan A. Rosado

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Constantin, B. (2016). Role of Scaffolding Proteins in the Regulation of TRPC-Dependent Calcium Entry. In: Rosado, J. (eds) Calcium Entry Pathways in Non-excitable Cells. Advances in Experimental Medicine and Biology, vol 898. Springer, Cham. https://doi.org/10.1007/978-3-319-26974-0_16

Download citation

Publish with us

Policies and ethics

Search

Navigation