Neurological and Motor Disorders: Neuronal Store-Operated Ca2+ Signaling: An Overview and Its Function

  • Sunitha BollimunthaEmail author
  • Biswaranjan Pani
  • Brij B. SinghEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 993)


Calcium (Ca2+) is a ubiquitous second messenger that performs significant physiological task such as neurosecretion, exocytosis, neuronal growth/differentiation, and the development and/or maintenance of neural circuits. An important regulatory aspect of neuronal Ca2+ homeostasis is store-operated Ca2+ entry (SOCE) which, in recent years, has gained much attention for influencing a variety of nerve cell responses. Essentially, activation of SOCE ensues following the activation of the plasma membrane (PM) store-operated Ca2+ channels (SOCC) triggered by the depletion of endoplasmic reticulum (ER) Ca2+ stores. In addition to the TRPC (transient receptor potential canonical) and the Orai family of ion channels, STIM (stromal interacting molecule) proteins have been baptized as key molecular regulators of SOCE. Functional significance of the TRPC channels in neurons has been elaborately studied; however, information on Orai and STIM components of SOCE, although seems imminent, is currently limited. Importantly, perturbations in SOCE have been implicated in a spectrum of neuropathological conditions. Hence, understanding the precise involvement of SOCC in neurodegeneration would presumably unveil avenues for plausible therapeutic interventions. We thus review the role of SOCE-regulated neuronal Ca2+ signaling in selecting neurodegenerative conditions.


TRPC Calcium Oxidative and ER stress Neurodegenerative diseases 



We duly acknowledge the grant support from the National Institutes of Health (DE017102; DE024300; GM113123).


  1. Aarts MM, Tymianski M (2005) TRPMs and neuronal cell death. Pflugers Arch 451:243–249PubMedCrossRefGoogle Scholar
  2. Adachi N, Kobayashi T, Takahashi H, Kawasaki T, Shirai Y, Ueyama T, Matsuda T, Seki T, Sakai N, Saito N (2008) Enzymological analysis of mutant protein kinase C gamma causing spinocerebellar ataxia type 14 and dysfunction in Ca2+ homeostasis. J Biol Chem 283:19854–19863PubMedCrossRefGoogle Scholar
  3. Agam K, von Campenhausen M, Levy S, Ben-Ami HC, Cook B, Kirschfeld K, Minke B (2000) Metabolic stress reversibly activates the Drosophila light-sensitive channels TRP and TRPL in vivo. J Neurosci 20:5748–5755PubMedGoogle Scholar
  4. Akbari Y, Hitt BD, Murphy MP, Dagher NN, Tseng BP, Green KN, Golde TE, LaFerla FM (2004) Presenilin regulates capacitative calcium entry dependently and independently of gamma-secretase activity. Biochem Biophys Res Commun 322:1145–1152PubMedCrossRefGoogle Scholar
  5. Albers DS, Beal MF (2000) Mitochondrial dysfunction and oxidative stress in aging and neurodegenerative disease. J Neural Transm Suppl 59:133–154PubMedGoogle Scholar
  6. 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 42:543–549PubMedCrossRefGoogle Scholar
  7. Banerjee S, Lee J, Venkatesh K, Wu CF, Hasan G (2004) Loss of flight and associated neuronal rhythmicity in inositol 1,4,5-trisphosphate receptor mutants of Drosophila. J Neurosci 24:7869–7878PubMedPubMedCentralCrossRefGoogle Scholar
  8. Barritt GJ (1999) Receptor-activated Ca2+ inflow in animal cells: a variety of pathways tailored to meet different intracellular Ca2+ signalling requirements. Biochem J 337(Pt 2):153–169PubMedPubMedCentralCrossRefGoogle Scholar
  9. Beck B, Lehen’kyi V, Roudbaraki M, Flourakis M, Charveron M, Bordat P, Polakowska R, Prevarskaya N, Skryma R (2008) TRPC channels determine human keratinocyte differentiation: new insight into basal cell carcinoma. Cell Calcium 43:492–505PubMedCrossRefGoogle Scholar
  10. Becker EB, Oliver PK, Glitsch MD, Banks GT, Achilli F, Hardy A, Nolan PM, Fisher EM, Davies KE (2009) A point mutation in TRPC3 causes abnormal Purkinje cell development and cerebellar ataxia in moonwalker mice. Proc Natl Acad Sci U S A 106:6706–6711PubMedPubMedCentralCrossRefGoogle Scholar
  11. Berna-Erro A, Braun A, Kraft R, Kleinschnitz C, Schuhmann MK, Stegner D, Wultsch T, Eilers J, Meuth SG, Stoll G, Nieswandt B (2009) STIM2 regulates capacitive Ca2+ entry in neurons and plays a key role in hypoxic neuronal cell death. Sci Signal 2(93):ra67PubMedCrossRefGoogle Scholar
  12. Berridge MJ (1995) Capacitative calcium entry. Biochem J 312(Pt 1):1–11PubMedPubMedCentralCrossRefGoogle Scholar
  13. Berridge MJ (1997) The AM and FM of calcium signalling. Nature 386:759–760PubMedCrossRefGoogle Scholar
  14. Berridge MJ (1998) Neuronal calcium signaling. Neuron 21:13–26PubMedCrossRefGoogle Scholar
  15. Berridge MJ (2012) Calcium signalling remodelling and disease. Biochem Soc Trans 40:297–309PubMedCrossRefGoogle Scholar
  16. Berridge MJ, Dupont G (1994) Spatial and temporal signalling by calcium. Curr Opin Cell Biol 6:267–274PubMedCrossRefGoogle Scholar
  17. Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1:11–21PubMedCrossRefGoogle Scholar
  18. Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: dynamics, homeostasis and remodeling. Nat Rev Mol Cell Biol 4:517–729PubMedCrossRefGoogle Scholar
  19. Bezprozvanny I, Hayden MR (2004) Deranged neuronal calcium signaling and Huntington disease. Biochem Biophys Res Commun 322:1310–1317PubMedCrossRefGoogle Scholar
  20. Bezprozvanny I, Mattson MP (2008) Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends Neurosci 31:454–463PubMedPubMedCentralCrossRefGoogle Scholar
  21. Birnbaumer L (2009) The TRPC class of ion channels: a critical review of their roles in slow, sustained increases in intracellular Ca(2+) concentrations. Annu Rev Pharmacol Toxicol 49:395–426PubMedCrossRefGoogle Scholar
  22. Bogeski I, Kummerow C, Al-Ansary D, Schwarz EC, Koehler R, Kozai D, Takahashi N, Peinelt C, Griesemer D, Bozem M, Mori Y, Hoth M, Niemeyer BA (2010) Differential redox regulation of ORAI ion channels: a mechanism to tune cellular calcium signaling. Sci Signal 3(115):ra24PubMedCrossRefGoogle Scholar
  23. Bojarski L, Pomorski P, Szybinska A, Drab M, Skibinska-Kijek A, Gruszczynska-Biegala J, Kuznicki J (2009) Presenilin-dependent expression of STIM proteins and dysregulation of capacitative Ca2+ entry in familial Alzheimer’s disease. Biochim Biophys Acta 1793:1050–1057PubMedCrossRefGoogle Scholar
  24. Bollimuntha S, Cornatzer E, Singh BB (2005a) Plasma membrane localization and function of TRPC1 is dependent on its interaction with beta-tubulin in retinal epithelium cells. Vis Neurosci 22:163–170PubMedPubMedCentralCrossRefGoogle Scholar
  25. Bollimuntha S, Singh BB, Shavali S, Sharma SK, Ebadi M (2005b) TRPC1-mediated inhibition of 1-methyl-4-phenylpyridinium ion neurotoxicity in human SH-SY5Y neuroblastoma cells. J Biol Chem 280:2132–2140PubMedCrossRefGoogle Scholar
  26. Bonavia R, Bajetto A, Barbero S, Albini A, Noonan DM, Schettini G (2001) HIV-1 Tat causes apoptotic death and calcium homeostasis alterations in rat neurons. Biochem Biophys Res Commun 288:301–308PubMedCrossRefGoogle Scholar
  27. Brini M, Carafoli E (2009) Calcium pumps in health and disease. Physiol Rev 89:1341–1378PubMedCrossRefGoogle Scholar
  28. 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 452:43–52PubMedCrossRefGoogle Scholar
  29. Cassarino DS, Fall CP, Swerdlow RH, Smith TS, Halvorsen EM, Miller SW, Parks JP, Parker WD Jr, Bennett JP Jr (1997) Elevated reactive oxygen species and antioxidant enzyme activities in animal and cellular models of Parkinson’s disease. Biochim Biophys Acta 1362:77–86PubMedCrossRefGoogle Scholar
  30. Chakraborti T, Das S, Mondal M, Roychoudhury S, Chakraborti S (1999) Oxidant, mitochondria and calcium: an overview. Cell Signal 11:77–85PubMedCrossRefGoogle Scholar
  31. Cheek TR, Thastrup O (1989) Internal Ca2+ mobilization and secretion in bovine adrenal chromaffin cells. Cell Calcium 10:213–221PubMedCrossRefGoogle Scholar
  32. Cheng KT, Liu X, Ong HL, Ambudkar IS (2008) Functional requirement for Orai1 in store-operated TRPC1-STIM1 channels. J Biol Chem 283:12935–12940PubMedPubMedCentralCrossRefGoogle Scholar
  33. Cheung KH, Shineman D, Muller M, Cardenas C, Mei L, Yang J, Tomita T, Iwatsubo T, Lee VM, Foskett JK (2008) Mechanism of Ca2+ disruption in Alzheimer’s disease by presenilin regulation of InsP3 receptor channel gating. Neuron 58:871–883PubMedPubMedCentralCrossRefGoogle Scholar
  34. Clapham DE (2007) Calcium signaling. Cell 131:1047–1058PubMedCrossRefGoogle Scholar
  35. Clementi E, Scheer H, Zacchetti D, Fasolato C, Pozzan T, Meldolesi J (1992) Receptor-activated Ca2+ influx. Two independently regulated mechanisms of influx stimulation coexist in neurosecretory PC12 cells. J Biol Chem 267:2164–2172PubMedGoogle Scholar
  36. Congar P, Leinekugel X, Ben-Ari Y, Crepel V (1997) A long-lasting calcium-activated nonselective cationic current is generated by synaptic stimulation or exogenous activation of group I metabotropic glutamate receptors in CA1 pyramidal neurons. J Neurosci 17:5366–5379PubMedGoogle Scholar
  37. Crouzin N, de Jesus Ferreira MC, Cohen-Solal C, Aimar RF, Vignes M, Guiramand J (2007) Alpha-tocopherol-mediated long-lasting protection against oxidative damage involves an attenuation of calcium entry through TRP-like channels in cultured hippocampal neurons. Free Radic Biol Med 42:1326–1337PubMedCrossRefGoogle Scholar
  38. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909PubMedCrossRefGoogle Scholar
  39. De Strooper B, Annaert W (2000) Proteolytic processing and cell biological functions of the amyloid precursor protein. J Cell Sci 113(Pt 11):1857–1870PubMedGoogle Scholar
  40. Doan TN, Gentry DL, Taylor AA, Elliott SJ (1994) Hydrogen peroxide activates agonist-sensitive Ca(2+)-flux pathways in canine venous endothelial cells. Biochem J 297(Pt 1):209–215PubMedPubMedCentralCrossRefGoogle Scholar
  41. Dulneva A, Lee S, Oliver PL, Di Gleria K, Kessler BM, Davies KE, Becker EB (2015) The mutant Moonwalker TRPC3 channel links calcium signaling to lipid metabolism in the developing cerebellum. Hum Mol Genet 24:4114–4125PubMedPubMedCentralCrossRefGoogle Scholar
  42. Durackova Z (2010) Some current insights into oxidative stress. Physiol Res 59:459–469PubMedGoogle Scholar
  43. Ehehalt R, Keller P, Haass C, Thiele C, Simons K (2003) Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J Cell Biol 160:113–123PubMedPubMedCentralCrossRefGoogle Scholar
  44. Emptage NJ, Reid CA, Fine A (2001) Calcium stores in hippocampal synaptic boutons mediate short-term plasticity, store-operated Ca2+ entry, and spontaneous transmitter release. Neuron 29:197–208PubMedCrossRefGoogle Scholar
  45. Ermak G, Davies KJ (2002) Calcium and oxidative stress: from cell signaling to cell death. Mol Immunol 38:713–721PubMedCrossRefGoogle Scholar
  46. Fabian A, Fortmann T, Dieterich P, Riethmuller C, Schon P, Mally S, Nilius B, Schwab A (2008) TRPC1 channels regulate directionality of migrating cells. Pflugers Arch 457:475–484PubMedCrossRefGoogle Scholar
  47. 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 441:179–185PubMedCrossRefGoogle Scholar
  48. 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 25:2687–2701PubMedCrossRefGoogle Scholar
  49. Fonfria E, Marshall IC, Benham CD, Boyfield I, Brown JD, Hill K, Hughes JP, Skaper SD, McNulty S (2004) TRPM2 channel opening in response to oxidative stress is dependent on activation of poly(ADP-ribose) polymerase. Br J Pharmacol 143:186–192PubMedPubMedCentralCrossRefGoogle Scholar
  50. Friel DD, Tsien RW (1992) A caffeine- and ryanodine-sensitive Ca2+ store in bullfrog sympathetic neurones modulates effects of Ca2+ entry on [Ca2+]i. J Physiol 450:217–246PubMedPubMedCentralCrossRefGoogle Scholar
  51. Gailly P (2002) New aspects of calcium signaling in skeletal muscle cells: implications in Duchenne muscular dystrophy. Biochim Biophys Acta 1600:38–44PubMedCrossRefGoogle Scholar
  52. Giacomello M, Barbiero L, Zatti G, Squitti R, Binetti G, Pozzan T, Fasolato C, Ghidoni R, Pizzo P (2005) Reduction of Ca2+ stores and capacitative Ca2+ entry is associated with the familial Alzheimer’s disease presenilin-2 T122R mutation and anticipates the onset of dementia. Neurobiol Dis 18:638–648PubMedCrossRefGoogle Scholar
  53. Gomez TM, Robles E, Poo M, Spitzer NC (2001) Filopodial calcium transients promote substrate-dependent growth cone turning. Science 291:1983–1987PubMedCrossRefGoogle Scholar
  54. Goonasekera SA, Davis J, Kwong JQ, Accornero F, Wei-LaPierre L, Sargent MA, Dirksen RT, Molkentin JD (2014) Enhanced Ca2+ influx from STIM1-Orai1 induces muscle pathology in mouse models of muscular dystrophy. Hum Mol Genet 23:3706–3715PubMedPubMedCentralCrossRefGoogle Scholar
  55. Gouaux E, Mackinnon R (2005) Principles of selective ion transport in channels and pumps. Science 310:1461–1465PubMedCrossRefGoogle Scholar
  56. Guerini D, Coletto L, Carafoli E (2005) Exporting calcium from cells. Cell Calcium 38:281–289PubMedCrossRefGoogle Scholar
  57. Gwack Y, Feske S, Srikanth S, Hogan PG, Rao A (2007) Signalling to transcription: store-operated Ca2+ entry and NFAT activation in lymphocytes. Cell Calcium 42:145–156PubMedCrossRefGoogle Scholar
  58. Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T, Yamada H, Shimizu S, Mori E, Kudoh J, Shimizu N, Kurose H, Okada Y, Imoto K, Mori Y (2002) LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell 9:163–173PubMedCrossRefGoogle Scholar
  59. Hatano T, Kubo S, Imai S, Maeda M, Ishikawa K, Mizuno Y, Hattori N (2007) Leucine-rich repeat kinase 2 associates with lipid rafts. Hum Mol Genet 16:678–690PubMedCrossRefGoogle Scholar
  60. Haughey NJ, Holden CP, Nath A, Geiger JD (1999) Involvement of inositol 1,4,5-trisphosphate-regulated stores of intracellular calcium in calcium dysregulation and neuron cell death caused by HIV-1 protein tat. J Neurochem 73:1363–1374PubMedCrossRefGoogle Scholar
  61. Henke N, Albrecht P, Bouchachia I, Ryazantseva M, Knoll K, Lewerenz J, Kaznacheyeva E, Maher P, Methner A (2013) The plasma membrane channel ORAI1 mediates detrimental calcium influx caused by endogenous oxidative stress. Cell Death Dis 4:e470PubMedPubMedCentralCrossRefGoogle Scholar
  62. Hilgemann DW, Yaradanakul A, Wang Y, Fuster D (2006) Molecular control of cardiac sodium homeostasis in health and disease. J Cardiovasc Electrophysiol 17(Suppl 1):S47–S56PubMedCrossRefGoogle Scholar
  63. 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 8:1003–1010PubMedCrossRefGoogle Scholar
  64. Jia Y, Zhou J, Tai Y, Wang Y (2007) TRPC channels promote cerebellar granule neuron survival. Nat Neurosci 10:559–567PubMedCrossRefGoogle Scholar
  65. Kamata H, Hirata H (1999) Redox regulation of cellular signalling. Cell Signal 11:1–14PubMedCrossRefGoogle Scholar
  66. Kirichok Y, Krapivinsky G, Clapham DE (2004) The mitochondrial calcium uniporter is a highly selective ion channel. Nature 427:360–364PubMedCrossRefGoogle Scholar
  67. Kraft R (2015) STIM and ORAI proteins in the nervous system. Channels (Austin) 9:245–252CrossRefGoogle Scholar
  68. LaFerla FM (2002) Calcium dyshomeostasis and intracellular signalling in Alzheimer’s disease. Nat Rev Neurosci 3:862–872PubMedCrossRefGoogle Scholar
  69. Lessard CB, Lussier MP, Cayouette S, Bourque G, Boulay G (2005) The overexpression of presenilin2 and Alzheimer’s-disease-linked presenilin2 variants influences TRPC6-enhanced Ca2+ entry into HEK293 cells. Cell Signal 17:437–445PubMedCrossRefGoogle Scholar
  70. Li ST, Matsushita M, Moriwaki A, Saheki Y, Lu YF, Tomizawa K, Wu HY, Terada H, Matsui H (2004) HIV-1 Tat inhibits long-term potentiation and attenuates spatial learning [corrected]. Ann Neurol 55:362–371PubMedCrossRefGoogle Scholar
  71. 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 U S A 104:4682–4687PubMedPubMedCentralCrossRefGoogle Scholar
  72. 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 105:2895–2900PubMedPubMedCentralCrossRefGoogle Scholar
  73. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795PubMedCrossRefGoogle Scholar
  74. Lin X, Antalffy B, Kang D, Orr HT, Zoghbi HY (2000) Polyglutamine expansion down-regulates specific neuronal genes before pathologic changes in SCA1. Nat Neurosci 3:157–163PubMedCrossRefGoogle Scholar
  75. Linden R (1994) The survival of developing neurons: a review of afferent control. Neuroscience 58:671–682PubMedCrossRefGoogle Scholar
  76. 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 15:1235–1241PubMedPubMedCentralCrossRefGoogle Scholar
  77. Lohmann C, Finski A, Bonhoeffer T (2005) Local calcium transients regulate the spontaneous motility of dendritic filopodia. Nat Neurosci 8:305–312PubMedCrossRefGoogle Scholar
  78. Majewski L, Kuznicki J (2015) SOCE in neurons: signaling or just refilling? Biochim Biophys Acta 1853:1940–1952PubMedCrossRefGoogle Scholar
  79. Mark MD, Schwitalla JC, Groemmke M, Herlitze S (2017) Keeping our calcium in balance to maintain our balance. Biochem Biophys Res Commun 483(4):1040–1050PubMedCrossRefGoogle Scholar
  80. Martin-Romero FJ, Ortiz-de-Galisteo JR, Lara-Laranjeira J, Dominguez-Arroyo JA, Gonzalez-Carrera E, Alvarez IS (2008) Store-operated calcium entry in human oocytes and sensitivity to oxidative stress. Biol Reprod 78:307–315PubMedCrossRefGoogle Scholar
  81. Masliah E, Ge N, Mucke L (1996) Pathogenesis of HIV-1 associated neurodegeneration. Crit Rev Neurobiol 10:57–67PubMedCrossRefGoogle Scholar
  82. Mattson MP (2007) Calcium and neurodegeneration. Aging Cell 6:337–350PubMedCrossRefGoogle Scholar
  83. Mattson MP, Haughey NJ, Nath A (2005) Cell death in HIV dementia. Cell Death Differ 12(Suppl 1):893–904PubMedCrossRefGoogle Scholar
  84. McNulty S, Fonfria E (2005) The role of TRPM channels in cell death. Pflugers Arch 451:235–242PubMedCrossRefGoogle Scholar
  85. Meldolesi J, Volpe P, Pozzan T (1988) The intracellular distribution of calcium. Trends Neurosci 11:449–452PubMedCrossRefGoogle Scholar
  86. Miller RJ (1988) Calcium signalling in neurons. Trends Neurosci 11:415–419PubMedCrossRefGoogle Scholar
  87. Miller BA (2004) Inhibition of TRPM2 function by PARP inhibitors protects cells from oxidative stress-induced death. Br J Pharmacol 143:515–516PubMedPubMedCentralCrossRefGoogle Scholar
  88. Miller BA (2006) The role of TRP channels in oxidative stress-induced cell death. J Membr Biol 209:31–41PubMedCrossRefGoogle Scholar
  89. Montell C (2005a) TRP channels in Drosophila photoreceptor cells. J Physiol 567:45–51PubMedPubMedCentralCrossRefGoogle Scholar
  90. Montell C (2005b) The TRP superfamily of cation channels. Sci STKE 2005:re3PubMedGoogle Scholar
  91. Nishiyama M, Hong K, Mikoshiba K, Poo MM, Kato K (2000) Calcium stores regulate the polarity and input specificity of synaptic modification. Nature 408:584–588PubMedCrossRefGoogle Scholar
  92. Norman JP, Perry SW, Kasischke KA, Volsky DJ, Gelbard HA (2007) HIV-1 trans activator of transcription protein elicits mitochondrial hyperpolarization and respiratory deficit, with dysregulation of complex IV and nicotinamide adenine dinucleotide homeostasis in cortical neurons. J Immunol 178:869–876PubMedCrossRefGoogle Scholar
  93. Norman JP, Perry SW, Reynolds HM, Kiebala M, De Mesy Bentley KL, Trejo M, Volsky DJ, Maggirwar SB, Dewhurst S, Masliah E, Gelbard HA (2008) HIV-1 Tat activates neuronal ryanodine receptors with rapid induction of the unfolded protein response and mitochondrial hyperpolarization. PLoS One 3:e3731PubMedPubMedCentralCrossRefGoogle Scholar
  94. Nunes P, Demaurex N (2014) Redox regulation of store-operated Ca2+ entry. Antioxid Redox Signal 21(6):915–932PubMedPubMedCentralCrossRefGoogle Scholar
  95. O’Bryant SE, Hobson V, Hall JR, Waring SC, Chan W, Massman P, Lacritz L, Cullum CM, Diaz-Arrastia R (2009) Brain-derived neurotrophic factor levels in Alzheimer’s disease. J Alzheimers Dis 17:337–341PubMedPubMedCentralCrossRefGoogle Scholar
  96. 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 282:9105–9116PubMedPubMedCentralCrossRefGoogle Scholar
  97. Pani B, Singh BB (2009) Lipid rafts/caveolae as microdomains of calcium signaling. Cell Calcium 45:625–633PubMedPubMedCentralCrossRefGoogle Scholar
  98. Pani B, Cornatzer E, Cornatzer W, Shin DM, Pittelkow MR, Hovnanian A, Ambudkar IS, Singh BB (2006) Up-regulation of transient receptor potential canonical 1 (TRPC1) following sarco(endo)plasmic reticulum Ca2+ ATPase 2 gene silencing promotes cell survival: a potential role for TRPC1 in Darier’s disease. Mol Biol Cell 17:4446–4458PubMedPubMedCentralCrossRefGoogle Scholar
  99. Parekh AB (2011) Decoding cytosolic Ca(2+) oscillations. Trends Biochem Sci 36(2):78–87PubMedCrossRefGoogle Scholar
  100. Parekh AB, Penner R (1997) Store depletion and calcium influx. Physiol Rev 77:901–930PubMedGoogle Scholar
  101. Park JY, Kim KS, Lee SB, Ryu JS, Chung KC, Choo YK, Jou I, Kim J, Park SM (2009) On the mechanism of internalization of alpha-synuclein into microglia: roles of ganglioside GM1 and lipid raft. J Neurochem 110:400–411PubMedCrossRefGoogle Scholar
  102. Parkin ET, Turner AJ, Hooper NM (1999) Amyloid precursor protein, although partially detergent-insoluble in mouse cerebral cortex, behaves as an atypical lipid raft protein. Biochem J 344(Pt 1):23–30PubMedPubMedCentralCrossRefGoogle Scholar
  103. Patten DA, Germain M, Kelly MA, Slack RS (2010) Reactive oxygen species: stuck in the middle of neurodegeneration. J Alzheimers Dis 20(Suppl 2):S357–S367PubMedCrossRefGoogle Scholar
  104. Peng F, Yao H, Akturk HK, Buch S (2012) Platelet-derived growth factor CC-mediated neuroprotection against HIV Tat involves TRPC-mediated inactivation of GSK 3beta. PLoS One 7(10):e47572PubMedPubMedCentralCrossRefGoogle Scholar
  105. Philipp S, Hambrecht J, Braslavski L, Schroth G, Freichel M, Murakami M, Cavalie A, Flockerzi V (1998) A novel capacitative calcium entry channel expressed in excitable cells. EMBO J 17:4274–4282PubMedPubMedCentralCrossRefGoogle Scholar
  106. Pizzo P, Burgo A, Pozzan T, Fasolato C (2001) Role of capacitative calcium entry on glutamate-induced calcium influx in type-I rat cortical astrocytes. J Neurochem 79:98–109PubMedCrossRefGoogle Scholar
  107. Poteser M, Graziani A, Rosker C, Eder P, Derler I, Kahr H, Zhu MX, Romanin C, Groschner K (2006) TRPC3 and TRPC4 associate to form a redox-sensitive cation channel. Evidence for expression of native TRPC3-TRPC4 heteromeric channels in endothelial cells. J Biol Chem 281:13588–13595PubMedCrossRefGoogle Scholar
  108. Przedborski S, Tieu K, Perier C, Vila M (2004) MPTP as a mitochondrial neurotoxic model of Parkinson’s disease. J Bioenerg Biomembr 36:375–379PubMedCrossRefGoogle Scholar
  109. Putney JW Jr (2003) Capacitative calcium entry in the nervous system. Cell Calcium 34:339–344PubMedCrossRefGoogle Scholar
  110. Putney JW Jr (2011) The physiological function of store-operated calcium entry. Neurochem Res 36:1157–1165PubMedPubMedCentralCrossRefGoogle Scholar
  111. Putney JW Jr (2013) Alternative forms of the store-operated calcium entry mediators, STIM1 and Orai1. Curr Top Membr 71:109–123PubMedCrossRefGoogle Scholar
  112. Putney JW, Bird GS (2008) Cytoplasmic calcium oscillations and store-operated calcium influx. J Physiol 586:3055–3059PubMedPubMedCentralCrossRefGoogle Scholar
  113. 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 169:435–445PubMedPubMedCentralCrossRefGoogle Scholar
  114. Sattler R, Tymianski M (2000) Molecular mechanisms of calcium-dependent excitotoxicity. J Mol Med 78:3–13PubMedCrossRefGoogle Scholar
  115. Self RL, Mulholland PJ, Nath A, Harris BR, Prendergast MA (2004) The human immunodeficiency virus type-1 transcription factor Tat produces elevations in intracellular Ca2+ that require function of an N-methyl-D-aspartate receptor polyamine-sensitive site. Brain Res 995:39–45PubMedCrossRefGoogle Scholar
  116. Selvaraj S, Watt JA, Singh BB (2009) TRPC1 inhibits apoptotic cell degeneration induced by dopaminergic neurotoxin MPTP/MPP(+). Cell Calcium 46:209–218PubMedPubMedCentralCrossRefGoogle Scholar
  117. Selvaraj S, Sun Y, Watt JA, Song S, Lei S, Birnbaumer L, Singh BB (2012) Toxin-induced ER stress in mice involves down regulation of TRPC1 and inhibition of the AKT/mTOR signaling. J Clin Invest 122:1354–1367PubMedPubMedCentralCrossRefGoogle Scholar
  118. Singh BB, Zheng C, Liu X, Lockwich T, Liao D, Zhu MX, Birnbaumer L, Ambudkar IS (2001) Trp1-dependent enhancement of salivary gland fluid secretion: role of store-operated calcium entry. FASEB J 15:1652–1654PubMedGoogle Scholar
  119. Strehler EE, Treiman M (2004) Calcium pumps of plasma membrane and cell interior. Curr Mol Med 4:323–335PubMedCrossRefGoogle Scholar
  120. Stutzmann GE, Smith I, Caccamo A, Oddo S, Laferla FM, Parker I (2006) Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young, adult, and aged Alzheimer’s disease mice. J Neurosci 26:5180–5189PubMedCrossRefGoogle Scholar
  121. Sukumaran P, Schaar A, Sun Y, Singh BB (2016) Functional role of TRP channels in modulating ER stress and autophagy. Cell Calcium 60(2):123–132PubMedPubMedCentralCrossRefGoogle Scholar
  122. Sun Y, Sukumaran P, Singh BB (2014a) Physiological function and characterization of TRPCs in non-excitable and excitable cells. Cells 3:455–475PubMedPubMedCentralCrossRefGoogle Scholar
  123. Sun S, Zhang H, Liu J, Popugaeva E, Xu NJ, Feske S, White CL, Bezprozvanny I (2014b) Reduced synaptic STIM2 expression and impaired store-operated calcium entry cause destabilization of mature spines in mutant presenilin mice. Neuron 82:79–93PubMedPubMedCentralCrossRefGoogle Scholar
  124. Tu H, Nelson O, Bezprozvanny A, Wang Z, Lee SF, Hao YH, Serneels L, De Strooper B, Yu G, Bezprozvanny I (2006) Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer’s disease-linked mutations. Cell 126:981–993PubMedPubMedCentralCrossRefGoogle Scholar
  125. 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 158:1089–1096PubMedPubMedCentralCrossRefGoogle Scholar
  126. Vandebrouck A, Ducret T, Basset O, Sebille S, Raymond G, Ruegg U, Gailly P, Cognard C, Constantin B (2006) Regulation of store-operated calcium entries and mitochondrial uptake by minidystrophin expression in cultured myotubes. FASEB J 20:136–138PubMedGoogle Scholar
  127. van de Leemput J, Chandran J, Knight MA, Holtzclaw LA, Scholz S, Cookson MR, Houlden H, Gwinn-Hardy K, Fung HC, Lin X, Hernandez D, Simon-Sanchez J, Wood NW, Giunti P, Rafferty I, Hardy J, Storey E, Gardner RJ, Forrest SM, Fisher EM, Russell JT, Cai H, Singleton AB (2007) Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans. PLoS Genet 3:e108PubMedPubMedCentralCrossRefGoogle Scholar
  128. Venkatachalam K, Montell C (2007) TRP channels. Annu Rev Biochem 76:387–417PubMedPubMedCentralCrossRefGoogle Scholar
  129. Venkiteswaran G, Hasan G (2009) Intracellular Ca2+ signaling and store-operated Ca2+ entry are required in Drosophila neurons for flight. Proc Natl Acad Sci U S A 106:10326–10331PubMedPubMedCentralCrossRefGoogle Scholar
  130. Vig PJ, Subramony SH, McDaniel DO (2001) Calcium homeostasis and spinocerebellar ataxia-1 (SCA-1). Brain Res Bull 56:221–225PubMedCrossRefGoogle Scholar
  131. Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP (2006) CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science 312:1220–1223PubMedCrossRefGoogle Scholar
  132. 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 279:43392–43402PubMedCrossRefGoogle Scholar
  133. Yamamoto S, Shimizu S, Mori Y (2009) Involvement of TRPM2 channel in amplification of reactive oxygen species-induced signaling and chronic inflammation. Nippon Yakurigaku Zasshi 134:122–126PubMedCrossRefGoogle Scholar
  134. Yang KT, Chang WL, Yang PC, Chien CL, Lai MS, Su MJ, Wu ML (2006) Activation of the transient receptor potential M2 channel and poly(ADP-ribose) polymerase is involved in oxidative stress-induced cardiomyocyte death. Cell Death Differ 13:1815–1826PubMedCrossRefGoogle Scholar
  135. Yao H, Peng F, Dhillon N, Callen S, Bokhari S, Stehno-Bittel L, Ahmad SO, Wang JQ, Buch S (2009a) Involvement of TRPC channels in CCL2-mediated neuroprotection against tat toxicity. J Neurosci 29:1657–1669PubMedPubMedCentralCrossRefGoogle Scholar
  136. Yao H, Peng F, Fan Y, Zhu X, Hu G, Buch SJ (2009b) TRPC channel-mediated neuroprotection by PDGF involves Pyk2/ERK/CREB pathway. Cell Death Differ 16:1681–1693PubMedPubMedCentralCrossRefGoogle Scholar
  137. Ye S, Tan L, Ma J, Shi Q, Li J (2010) Polyunsaturated docosahexaenoic acid suppresses oxidative stress induced endothelial cell calcium influx by altering lipid composition in membrane caveolar rafts. Prostaglandins Leukot Essent Fatty Acids 83:37–43PubMedCrossRefGoogle Scholar
  138. Yoo AS, Cheng I, Chung S, Grenfell TZ, Lee H, Pack-Chung E, Handler M, Shen J, Xia W, Tesco G, Saunders AJ, Ding K, Frosch MP, Tanzi RE, Kim TW (2000) Presenilin-mediated modulation of capacitative calcium entry. Neuron 27:561–572PubMedCrossRefGoogle Scholar
  139. Yoshida T, Inoue R, Morii T, Takahashi N, Yamamoto S, Hara Y, Tominaga M, Shimizu S, Sato Y, Mori Y (2006) Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nat Chem Biol 2:596–607PubMedCrossRefGoogle Scholar
  140. 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 11:337–343PubMedPubMedCentralCrossRefGoogle Scholar
  141. 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 32:439–448PubMedPubMedCentralCrossRefGoogle Scholar
  142. 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 85:661–671PubMedCrossRefGoogle Scholar
  143. Zuccato C, Cattaneo E (2007) Role of brain-derived neurotrophic factor in Huntington’s disease. Prog Neurobiol 81:294–330PubMedCrossRefGoogle Scholar
  144. Zuccato C, Cattaneo E (2009) Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 5:311–322PubMedCrossRefGoogle Scholar

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Biomedical Sciences, School of Medicine and Health SciencesUniversity of North DakotaGrand ForksUSA

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