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Tissue Specificity: The Role of Organellar Membrane Nanojunctions in Smooth Muscle Ca2+ Signaling

  • Nicola FameliEmail author
  • A. Mark Evans
  • Cornelis van BreemenEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 993)

Abstract

In this chapter we examine the importance of cytoplasmic nanojunctions—nanometer scale appositions between organellar membranes including the molecular transporters therein—to the cell signaling machinery, with specific reference to Ca2+ transport and signaling in vascular smooth muscle and endothelial cells. More specifically, we will consider the extent to which quantitative modeling may aid in the development of our understanding of these processes. Testament to the requirement for such approaches lies in the fact that recent studies have provided evermore convincing evidence in support of the view that cytoplasmic nanospaces may be as significant to the process of Ca2+ signaling as the Ca2+ transporters, release channels, and Ca2+-storing organelles themselves. Moreover, the disruption and/or dysfunction of cytoplasmic nanospaces may be central to the origin of certain diseases. By way of introduction, we provide a historical perspective on the identification of smooth muscle cell plasma membrane (PM)-sarcoplasmic reticulum (SR) nanospaces and the early evidence in support of their role in the generation of asynchronous Ca2+ waves. We then summarize how stochastic modeling approaches can aid and guide the development of our understanding of two basic functional steps leading to healthy smooth muscle cell contraction. We furthermore outline how more sophisticated and realistic quantitative stochastic modeling may be employed not only to test working hypotheses, but also to lead in their development in a manner that informs further experimental investigation. Finally, we consider more recently defined nanospaces such as the lysosome-SR junction, by way of demonstrating the importance of quantitative stochastic modeling to our understanding of signaling mechanisms.

Keywords

Cytoplasmic nanojunctions ER junctions Calcium signaling Smooth muscle Endothelium Lysosomes Stochastic modeling 

Supplementary material

In this animation, we start from an extracellular view of one PM-SR nanospace. The PM is depicted in red. The light blue/green object is part of the SR. The dark blue hemispheres on it represent SERCA pumps and the yellow objects on the PM represent NCX. The white sphere within the nanospace is one Ca2+ undergoing three-dimensional random-walk motion. As the animation progresses, we are flying under the PM and inside the space between the PM and SR membrane and eventually out again. All the elements in this model are to scale, except for Ca2+, whose radius is ten times its Bohr radius for visibility (MPG 8720 kb)

References

  1. Andrews SS, Addy NJ, Brent R, Arkin AP (2010) Detailed simulations of cell biology with Smoldyn 2.1. PLoS Comput Biol 6(3):e1000705Google Scholar
  2. Beard NA, Sakowska MM, Dulhunty AF, Laver DR (2002) Calsequestrin is an inhibitor of skeletal muscle ryanodine receptor calcium release channels. Biophys J 82(1 Pt 1):310–320CrossRefPubMedPubMedCentralGoogle Scholar
  3. Berra-Romani R, Mazzocco-Spezzia A, Pulina MV, Golovina VA (2008) Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture. Am J Physiol Cell Physiol 295(3):C779–C790CrossRefPubMedPubMedCentralGoogle Scholar
  4. Blaustein MP, Lederer WJ (1999) Sodium/calcium exchange: its physiological implications. Physiol Rev 79(3):763–854PubMedGoogle Scholar
  5. Blender (2016) blender.org—Home. Available at: http://www.blender.org/
  6. Boittin F, Galione A, Evans AM (2002) Nicotinic acid adenine dinucleotide phosphate mediates Ca2+ signals and contraction in arterial smooth muscle via a two-pool mechanism. Circ Res 91(12):1168–1175CrossRefPubMedGoogle Scholar
  7. Boittin FX, Dipp M, Kinnear NP, Galione A, Evans AM (2003) Vasodilation by the calcium-mobilizing messenger cyclic ADP-ribose. J Biol Chem 278(11):9602–9608CrossRefPubMedGoogle Scholar
  8. Boulianne L, Al Assaad S, Dumontier M, Gross WJ (2008) GridCell: a stochastic particle-based biological system simulator. BMC Syst Biol 2:66CrossRefPubMedPubMedCentralGoogle Scholar
  9. Calcraft PJ, Ruas M, Pan Z, Cheng X, Arredouani A, Hao X, Tang J, Rietdorf K, Teboul L, Chuang KT, Lin P, Xiao R, Wang C, Zhu Y, Lin Y, Wyatt CN, Parrington J, Ma J, Evans AM, Galione A, Zhu MX (2009) NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature 459(7246):596–600CrossRefPubMedPubMedCentralGoogle Scholar
  10. Carstea ED, Morris JA, Coleman KG, Loftus SK, Zhang D, Cummings C, Gu J, Rosenfeld MA, Pavan WJ, Krizman DB, Nagle J, Polymeropoulos MH, Sturley SL, Ioannou YA, Higgins ME, Comly M, Cooney A, Brown A, Kaneski CR, Blanchette-Mackie EJ, Dwyer NK, Neufeld EB, Chang TY, Liscum L, Strauss JF 3rd, Ohno K, Zeigler M, Carmi R, Sokol J, Markie D, O’Neill RR, van Diggelen OP, Elleder M, Patterson MC, Brady RO, Vanier MT, Pentchev PG, Tagle DA (1997) Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science 277(5323):228–231CrossRefPubMedGoogle Scholar
  11. ChemCell (2016) Available at: http://www.sandia.gov/
  12. Chen SR, Li X, Ebisawa K, Zhang L (1997) Functional characterization of the recombinant type 3 Ca2+ release channel (ryanodine receptor) expressed in HEK293 cells. J Biol Chem 272(39):24234–24246CrossRefPubMedGoogle Scholar
  13. Ching LL, Williams AJ, Sitsapesan R (2000) Evidence for Ca(2+) activation and inactivation sites on the luminal side of the cardiac ryanodine receptor complex. Circ Res 87(3):201–206CrossRefPubMedGoogle Scholar
  14. Clark JH, Kinnear NP, Kalujnaia S, Cramb G, Fleischer S, Jeyakumar LH, Wuytack F, Evans AM (2010) Identification of functionally segregated sarcoplasmic reticulum calcium stores in pulmonary arterial smooth muscle. J Biol Chem 285(18):13542–13549CrossRefPubMedPubMedCentralGoogle Scholar
  15. Dai JM, Syyong H, Navarro-Dorado J, Redondo S, Alonso M, van Breemen C, Tejerina T (2010) A comparative study of alpha-adrenergic receptor mediated Ca(2+) signals and contraction in intact human and mouse vascular smooth muscle. Eur J Pharmacol 629(1–3):82–88CrossRefPubMedGoogle Scholar
  16. Demaurex N, Distelhorst C (2003) Cell biology. Apoptosis—the calcium connection. Science 300(5616):65–67CrossRefPubMedGoogle Scholar
  17. Devine CE, Somlyo AV, Somlyo AP (1972) Sarcoplasmic reticulum and excitation-contraction coupling in mammalian smooth muscles. J Cell Biol 52(3):690–718CrossRefPubMedPubMedCentralGoogle Scholar
  18. Di Giuro CML, Shrestha N, Malli R, Groschner K, van Breemen C, Fameli N (2016) Na+/Ca2+ exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca2+ via ER nanojunctions in vascular endothelial cells. bioRxiv. Available at: https://doi.org/10.1101/084285
  19. Dode L, Andersen JP, Leslie N, Dhitavat J, Vilsen B, Hovnanian A (2003) Dissection of the functional differences between sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 1 and 2 isoforms and characterization of Darier disease (SERCA2) mutants by steady-state and transient kinetic analyses. J Biol Chem 278(48):47877–47889CrossRefPubMedGoogle Scholar
  20. Elmoselhi AB, Blennerhassett M, Samson SE, Grover AK (1995) Properties of the sarcoplasmic reticulum Ca(2+)-pump in coronary artery skinned smooth muscle. Mol Cell Biochem 151(2):149–155CrossRefPubMedGoogle Scholar
  21. Evans AM, Fameli N, Ogunbayo OA, Duan J, Navarro-Dorado J (2016) From contraction to gene expression: nanojunctions of the sarco/endoplasmic reticulum deliver site- and function-specific calcium signals. Sci China Life Sci 59(8):749–763CrossRefPubMedGoogle Scholar
  22. Fameli N, van Breemen C, Kuo K (2007) A quantitative model for linking Na+/Ca2+ exchanger to SERCA during refilling of the sarcoplasmic reticulum to sustain [Ca2+] oscillations in vascular smooth muscle. Cell Calcium 42(6):565–575CrossRefPubMedGoogle Scholar
  23. Fameli N, Kuo K, van Breemen C (2009) A model for the generation of localized transient [Na+] elevations in vascular smooth muscle. Biochem Biophys Res Commun 389(3):461–465CrossRefPubMedGoogle Scholar
  24. Fameli N, Ogunbayo OA, van Breemen C, Evans AM (2014) Cytoplasmic nanojunctions between lysosomes and sarcoplasmic reticulum are required for specific calcium signaling. F1000Res 3:93PubMedPubMedCentralGoogle Scholar
  25. Gabella G (1971) Caveolae intracellulares and sarcoplasmic reticulum in smooth muscle. J Cell Sci 8(3):601–609PubMedGoogle Scholar
  26. Gilchrist JS, Belcastro AN, Katz S (1992) Intraluminal Ca2+ dependence of Ca2+ and ryanodine-mediated regulation of skeletal muscle sarcoplasmic reticulum Ca2+ release. J Biol Chem 267(29):20850–20856PubMedGoogle Scholar
  27. Gozuacik D, Kimchi A (2004) Autophagy as a cell death and tumor suppressor mechanism. Oncogene 23(16):2891–2906CrossRefPubMedGoogle Scholar
  28. Györke I, Györke S (1998) Regulation of the cardiac ryanodine receptor channel by luminal Ca2+ involves luminal Ca2+ sensing sites. Biophys J 75(6):2801–2810CrossRefPubMedPubMedCentralGoogle Scholar
  29. Holmes ME, Samson SE, Wilson JX, Dixon SJ, Grover AK (2000) Ascorbate transport in pig coronary artery smooth muscle: Na(+) removal and oxidative stress increase loss of accumulated cellular ascorbate. J Vasc Res 37(5):390–398CrossRefPubMedGoogle Scholar
  30. Iino M, Kasai H, Yamazawa T (1994) Visualization of neural control of intracellular Ca2+ concentration in single vascular smooth muscle cells in situ. EMBO J 13(21):5026–5031PubMedPubMedCentralGoogle Scholar
  31. Inesi G, Sumbilla C, Kirtley ME (1990) Relationships of molecular structure and function in Ca2(+)-transport ATPase. Physiol Rev 70(3):749–760PubMedGoogle Scholar
  32. Iversen LL (1973) Catecholamine uptake processes. Br Med Bull 29(2):130–135CrossRefPubMedGoogle Scholar
  33. Jmoudiak M, Futerman AH (2005) Gaucher disease: pathological mechanisms and modern management. Br J Haematol 129(2):178–188CrossRefPubMedGoogle Scholar
  34. Kinnear NP, Boittin FX, Thomas JM, Galione A, Evans AM (2004) Lysosome-sarcoplasmic reticulum junctions. A trigger zone for calcium signaling by nicotinic acid adenine dinucleotide phosphate and endothelin-1. J Biol Chem 279(52):54319–54326CrossRefPubMedGoogle Scholar
  35. Kinnear NP, Wyatt CN, Clark JH, Calcraft PJ, Fleischer S, Jeyakumar LH, Nixon GF, Evans AM (2008) Lysosomes co-localize with ryanodine receptor subtype 3 to form a trigger zone for calcium signalling by NAADP in rat pulmonary arterial smooth muscle. Cell Calcium 44(2):190–201CrossRefPubMedPubMedCentralGoogle Scholar
  36. Läuger P (1991) Electrogenic ion pumps. Sinauer, Sunderland, MAGoogle Scholar
  37. Lee CH, Poburko D, Sahota P, Sandhu J, Ruehlmann DO, van Breemen C (2001) The mechanism of phenylephrine-mediated [Ca(2+)](i) oscillations underlying tonic contraction in the rabbit inferior vena cava. J Physiol 534(Pt 3):641–650CrossRefPubMedPubMedCentralGoogle Scholar
  38. Lee CH, Poburko D, Kuo KH, Seow CY, van Breemen C (2002) Ca(2+) oscillations, gradients, and homeostasis in vascular smooth muscle. Am J Physiol Heart Circ Physiol 282(5):H1571–H1583CrossRefPubMedGoogle Scholar
  39. Lee CH, Kuo KH, Dai J, Leo JM, Seow CY, Breemen Cv (2005) Calyculin-A disrupts subplasmalemmal junction and recurring Ca2+ waves in vascular smooth muscle. Cell Calcium 37(1):9–16Google Scholar
  40. Lemos VS, Poburko D, Liao CH, Cole WC, van Breemen C (2007) Na+ entry via TRPC6 causes Ca2+ entry via NCX reversal in ATP stimulated smooth muscle cells. Biochem Biophys Res Commun 352(1):130–134CrossRefPubMedGoogle Scholar
  41. Li P, Chen SR (2001) Molecular basis of Ca(2)+ activation of the mouse cardiac Ca(2)+ release channel (ryanodine receptor). J Gen Physiol 118(1):33–44CrossRefPubMedPubMedCentralGoogle Scholar
  42. Lindemann JP, Jones LR, Hathaway DR, Henry BG, Watanabe AM (1983) beta-Adrenergic stimulation of phospholamban phosphorylation and Ca2+-ATPase activity in guinea pig ventricles. J Biol Chem 258(1):464–471PubMedGoogle Scholar
  43. Lloyd-Evans E, Morgan AJ, He X, Smith DA, Elliot-Smith E, Sillence DJ, Churchill GC, Schuchman EH, Galione A, Platt FM (2008) Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat Med 14(11):1247–1255CrossRefPubMedGoogle Scholar
  44. Magnier C, Papp B, Corvazier E, Bredoux R, Wuytack F, Eggermont J, Maclouf J, Enouf J (1992) Regulation of sarco-endoplasmic reticulum Ca(2+)-ATPases during platelet-derived growth factor-induced smooth muscle cell proliferation. J Biol Chem 267(22):15808–15815PubMedGoogle Scholar
  45. Malli R, Frieden M, Hunkova M, Trenker M, Graier WF (2007) Ca2+ refilling of the endoplasmic reticulum is largely preserved albeit reduced Ca2+ entry in endothelial cells. Cell Calcium 41(1):63–76CrossRefPubMedGoogle Scholar
  46. MCell (2016) MCell Home|Center for Quantitative Biological Simulation. Available at: http://mcell.org/
  47. Moore ED, Wasteneys GO (2012) Nanospace biophysics. Editorial. Protoplasma 249(Suppl 1):S1CrossRefPubMedGoogle Scholar
  48. Morgan AJ, Davis LC, Wagner SK, Lewis AM, Parrington J, Churchill GC, Galione A (2013) Bidirectional Ca2+ signaling occurs between the endoplasmic reticulum and acidic organelles. J Cell Biol 200(6):789–805CrossRefPubMedPubMedCentralGoogle Scholar
  49. Noori S, Acherman R, Siassi B, Luna C, Ebrahimi M, Pavlova Z, Ramanathan R (2002) A rare presentation of Pompe disease with massive hypertrophic cardiomyopathy at birth. J Perinat Med 30(6):517–521CrossRefPubMedGoogle Scholar
  50. Odermatt A, Kurzydlowski K, MacLennan DH (1996) The vmax of the Ca2+-ATPase of cardiac sarcoplasmic reticulum (SERCA2a) is not altered by Ca2+/calmodulin-dependent phosphorylation or by interaction with phospholamban. J Biol Chem 271(24):14206–14213CrossRefPubMedGoogle Scholar
  51. Paltauf-Doburzynska J, Posch K, Paltauf G, Graier WF (1998) Stealth ryanodine-sensitive Ca2+ release contributes to activity of capacitative Ca2+ entry and nitric oxide synthase in bovine endothelial cells. J Physiol 513(Pt 2):369–379CrossRefPubMedPubMedCentralGoogle Scholar
  52. 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(5):876–890CrossRefPubMedPubMedCentralGoogle Scholar
  53. Poburko D, Liao CH, Lemos VS, Lin E, Maruyama Y, Cole WC, van Breemen C (2007) Transient receptor potential channel 6-mediated, localized cytosolic [Na+] transients drive Na+/Ca2+ exchanger-mediated Ca2+ entry in purinergically stimulated aorta smooth muscle cells. Circ Res 101(10):1030–1038CrossRefPubMedGoogle Scholar
  54. Poburko D, Fameli N, Kuo KH, van Breemen C (2008) Ca2+ signaling in smooth muscle: TRPC6, NCX and LNats in nanodomains. Channels (Austin) 2(1):10–12CrossRefGoogle Scholar
  55. Poburko D, Liao CH, van Breemen C, Demaurex N (2009) Mitochondrial regulation of sarcoplasmic reticulum Ca2+ content in vascular smooth muscle cells. Circ Res 104(1):104–112CrossRefPubMedGoogle Scholar
  56. PW Workshop (2010) Nanospace biophysics. Available at: http://pwias.ubc.ca/profile/edwin-moore
  57. Raeymaekers L, Eggermont JA, Wuytack F, Casteels R (1990) Effects of cyclic nucleotide dependent protein kinases on the endoplasmic reticulum Ca2+ pump of bovine pulmonary artery. Cell Calcium 11(4):261–268CrossRefPubMedGoogle Scholar
  58. Rizzuto R, Duchen MR, Pozzan T (2004) Flirting in little space: the ER/mitochondria Ca2+ liaison. Sci STKE 2004(215):re1PubMedGoogle Scholar
  59. Ron I, Horowitz M (2008) Intracellular cholesterol modifies the ERAD of glucocerebrosidase in Gaucher disease patients. Mol Genet Metab 93(4):426–436CrossRefPubMedGoogle Scholar
  60. Smoldyn (2016) Available at: http://www.smoldyn.org
  61. Stiles JR, Bartol TM (2001) Monte Carlo methods for simulating realistic synaptic microphysiology using MCell. In: De Schutter E (ed) Computational neuroscience: realistic modeling for experimentalists. CRC, Boca Raton, pp 87–127Google Scholar
  62. Stiles JR, Van Helden D, Bartol TM Jr, Salpeter EE, Salpeter MM (1996) Miniature endplate current rise times less than 100 microseconds from improved dual recordings can be modeled with passive acetylcholine diffusion from a synaptic vesicle. Proc Natl Acad Sci USA 93(12):5747–5752CrossRefPubMedPubMedCentralGoogle Scholar
  63. Thorne GD, Paul RJ (2003) Effects of organ culture on arterial gene expression and hypoxic relaxation: role of the ryanodine receptor. Am J Physiol Cell Physiol 284(4):C999–C1005CrossRefPubMedGoogle Scholar
  64. Tripathy A, Meissner G (1996) Sarcoplasmic reticulum lumenal Ca2+ has access to cytosolic activation and inactivation sites of skeletal muscle Ca2+ release channel. Biophys J 70(6):2600–2615CrossRefPubMedPubMedCentralGoogle Scholar
  65. van Breemen C (1977) Calcium requirement for activation of intact aortic smooth muscle. J Physiol 272(2):317–329CrossRefPubMedPubMedCentralGoogle Scholar
  66. van Breemen C, Saida K (1989) Cellular mechanisms regulating [Ca2+]i smooth muscle. Annu Rev Physiol 51:315–329CrossRefPubMedGoogle Scholar
  67. van Breemen C, Lukeman S, Leijten P, Yamamoto H, Loutzenhiser R (1986) The role of superficial SR in modulating force development induced by Ca entry into arterial smooth muscle. J Cardiovasc Pharmacol 8(Suppl 8):S111–S116CrossRefPubMedGoogle Scholar
  68. van Breemen C, Fameli N, Evans AM (2013) Pan-junctional sarcoplasmic reticulum in vascular smooth muscle: nanospace Ca2+ transport for site- and function-specific Ca2+ signalling. J Physiol 591(8):2043–2054CrossRefPubMedPubMedCentralGoogle Scholar
  69. Verboomen H, Wuytack F, Van den Bosch L, Mertens L, Casteels R (1994) The functional importance of the extreme C-terminal tail in the gene 2 organellar Ca(2+)-transport ATPase (SERCA2a/b). Biochem J 303(Pt 3):979–984CrossRefPubMedPubMedCentralGoogle Scholar
  70. Wang IY, Bai Y, Sanderson MJ, Sneyd J (2010) A mathematical analysis of agonist- and KCl-induced Ca(2+) oscillations in mouse airway smooth muscle cells. Biophys J 98(7):1170–1181CrossRefPubMedPubMedCentralGoogle Scholar
  71. Wray S, Burdyga T (2010) Sarcoplasmic reticulum function in smooth muscle. Physiol Rev 90(1):113–178CrossRefPubMedGoogle Scholar
  72. Tassoni JP Jr, Fawaz KA, Johnston DE (1991) Cirrhosis and portal hypertension in a patient with adult Niemann-Pick disease. Gastroenterology 100(2):567–569CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Institute of BiophysicsMedical University of GrazGrazAustria
  2. 2.Department of Anesthesiology, Pharmacology and TherapeuticsThe University of British ColumbiaVancouverCanada
  3. 3.Centre for Integrative Physiology, College of Medicine and Veterinary MedicineUniversity of EdinburghEdinburghUK

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