Abstract
Dysregulated calcium signaling and accumulation of aberrant proteins causing endoplasmic reticulum stress are the early sign of intra-axonal pathological events in many neurodegenerative diseases, and apoptotic signaling is initiated when the stress goes beyond the maximum threshold level of endoplasmic reticulum. The fate of the cell to undergo apoptosis is controlled by Ca2+ signaling and dynamics at the level of the endoplasmic reticulum. Endoplasmic reticulum resident inositol 1,4,5-trisphosphate receptors (IP3R) play a pivotal role in cell death signaling by mediating Ca2+ flux from the endoplasmic reticulum into the cytosol and mitochondria. Hence, many prosurvival and prodeath signaling pathways and proteins affect Ca2+ signaling by directly targeting IP3R channels, which can happen in an IP3R-isoform-dependent manner. Here, in this review, we summarize the regulatory mechanisms of inositol triphosphate receptors in calcium regulation and initiation of apoptosis during unfolded protein response.
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Alzayady KJ, Wagner LE 2nd, Chandrasekhar R, Monteagudo A, Godiska R, Tall GG, Joseph SK, Yule DI (2013) Functional inositol 1,4,5-trisphosphate receptors assembled from concatenated homo- and heteromeric subunits. J Biol Chem 288:29772–29784
Anyatonwu G, Khan MT, Schug ZT, da Fonseca PC, Morris EP, Joseph SK (2010) Calcium-dependent conformational changes in inositol trisphosphate receptors. J Biol Chem 285:25085–25093
Arduino DM, Esteves AR, Cardoso SM, Oliveira CR (2009) Endoplasmic reticulum and mitochondria interplay mediates apoptotic cell death relevance to Parkinson’s disease. Neurochem Int 55:341–348
Bai GR, Yang LH, Huang XY, Sun FZ (2006) Inositol 1, 4, 5-trisphosphate receptor type 1phosphorylation and regulation by extracellular signal-regulated kinase. Biochem Biophys Res Commun 348:1319–1327
Betzenhauser MJ, Yule DI (2010) Regulation of inositol 1,4,5-trisphosphate receptors by phosphorylation and adenine nucleotides. Curr Top Membr 66:273–298
Betzenhauser MJ, Wagner LE 2nd, Iwai M, Michikawa T, Mikoshiba K, Yule DI (2008) ATP modulation of Ca2+ release by type-2 and type-3 inositol 1,4,5-triphosphate receptors. Differing ATP sensitivities and molecular determinants of action. J Biol Chem 283:21579–21587
Betzenhauser MJ, Fike JL, Wagner LE 2nd, Yule DI (2009a) Protein kinase A increases type-2 inositol 1,4,5-trisphosphate receptor activity by phosphorylation of serine 937. J Biol Chem 284:25116–25125
Betzenhauser MJ, Wagner LE 2nd, Park HS, Yule DI (2009b) ATP regulation of type-1 inositol 1,4,5-trisphosphate receptor activity does not require walker A type ATP binding motifs. J Biol Chem 284:16156–16163
Bezprozvanny I (2005) The inositol 1,4,5-trisphosphate receptors. Cell Calcium 38:261–272
Bezprozvanny I, Ehrlich BE (1993) ATP modulates the function of inositol 1,4,5-trisphosphate-gated channels at two sites. Neuron 10:1175–1184
Bezprozvanny I, Mattson MP (2008) Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease. Trends Neurosci 31:454–463
Bird GS, Burgess GM, Putney JW Jr (1993) Sulfhydryl reagents and cAMP-dependent kinase increase the sensitivity of the inositol 1,4,5-trisphosphate receptor in hepatocytes. J Biol Chem 268:17917–17923
Boehning D, Joseph SK (2000) Direct association of ligand-binding and pore domains in homo- and heterotetrameric inositol 1,4,5-trisphosphate receptors. EMBO J19:5450–5459
Boehning D, Mak DO, Foskett JK, Joseph SK (2001) Molecular determinants of ion permeation and selectivity in inositol 1,4,5-trisphosphate receptor Ca2+ channels. J Biol Chem 276:13509–13512
Bootman MD, Taylor CW, Berridge MJ (1992) The thiol reagent, thimerosal, evokes Ca2+ spikes in HeLa cells by sensitizing the inositol 1,4,5-trisphosphate receptor. J Biol Chem 267:25113–25119
Bosanac I, Michikawa T, Mikoshiba K, Ikura M (2004) Structural insights into the regulatory mechanism of IP3 receptor. Biochim Biophys Acta 1742:89–102
Bosanac I, Yamazaki H, Matsu-Ura T, Michikawa T, Mikoshiba K, Ikura M (2005) Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor. Mol Cell 17:193–203
Breckenridge D, Germain M, Mathai JP, Nguyen M, Shore GC (2003) Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 22:8608–8618
Bultynck G, Szlufcik K, Kasri NN, Assefa Z, Callewaert G, Missiaen L, Parys JB, De Smedt H (2004) Thimerosal stimulates Ca2+ flux through inositol 1,4,5-trisphosphate receptor type-1, but not type-3, via modulation of an isoform-specific Ca2+-dependent intramolecular interaction. Biochem J 381:87–96
Caroppo R, Colella M, Colasuonno A, DeLuisi A, Debellis L, Curci S, Hofer AM (2003) A reassessment of the effects of luminal [Ca2+] on inositol 1,4,5-trisphosphateinduced Ca2+ release from internal stores. J Biol Chem 278:39503–39508
Chaloux B, Caron AZ, Guillemette G (2007) Protein kinase A increases the binding affinity and the Ca2+ release activity of the inositol 1,4,5-trisphosphate receptor type 3 in RINm5F cells. Biol Cell 99:379–388
Chan J, Yamazaki H, Ishiyama N, Seo MD, Mal TK, Michikawa T, Mikoshiba K, Ikura M (2010) Structural studies of inositol 1,4,5-trisphosphate receptor: coupling ligand binding to channel gating. J Biol Chem 285:36092–36099
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 58:871–883
Cheung KH, Mei L, Mak DO, Hayashi I, Iwatsubo T, Kang DE, Foskett JK (2010) Gain of function enhancement of IP3 receptor modal gating by familial Alzheimer's disease-linked presenilin mutants in human cells and mouse neurons. Sci Signal 3:ra22
Chevalier-Larsen E, Holzbaur ELF (2006) Axonal transport and neurodegenerative disease. Biochim Biophys Acta 1762:1094–1108
Chiesa R, Piccardo P, Dossena S, Nowoslawski L, Roth KA, Ghetti B, Harris DA (2005) Bax deletion prevents neuronal loss but not neurological symptoms in a transgenic model of inherited prion disease. Proc Natl Acad Sci U S A 102:238–243
Clinton J, Forsyth C, Royston MC, Roberts GW (1993) Synaptic degeneration is the primary neuropathological feature in prion disease: a preliminary study. Neuroreport 4:65–68
Cunningham C, Deacon R, Wells H, Boche D, Waters S, Picanco DC, Scott H, Rawlins JNP, Perry V (2003) H.Synaptic changes characterize early behavioral signs in the ME7 model of murine prion disease. Eur J Neurosci 17:2147–2155
Danoff SK, Ferris CD, Donath C, Fischer GA, Munemitsu S, Ullrich A, Snyder SH, Ross CA (1991) Inositol 1,4,5-trisphosphate receptors: distinct neuronal and nonneuronal forms derived by alternative splicing differ in phosphorylation. Proc Natl Acad Sci U S A 88:2951–2955
Etcheberrigaray R, Hirashima N, Nee L, Prince J, Govoni S, Racchi M, Tanzi RE, Alkon DL (1998) Calcium responses in fibroblasts from asymptomatic members of Alzheimer's disease families. Neurobiol Dis 5:37–45
Ferreiro E, Resende R, Costa R, Oliveira CR, Pereira CMF (2006) An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity. Neurobiol Dis 23:669–678
Finch EA, Turner TJ, Goldin SM (1991) Calcium as a coagonist of inositol 1,4,5-Flynn, G.C., Pohl, J., Flocco, M.T. & Rothman, J.E., “Peptide-binding specificity of the molecular chaperone BiP”. Nature 353(6346):726–730
Foskett JK, Mak DO (2004) Novel model of calcium and inositol 1,4,5-trisphosphate regulation of InsP3 receptor channel gating in native endoplasmic reticulum. Biol Res 37:513–519
Foskett JK, White C, Cheung KH, Mak DO (2007) Inositol trisphosphate receptor Ca2 + release channels. Physiol Rev 87:593–658
Goldstein LS (2003) Do disorders of movement cause movement disorders and dementia? Neuron 40:415–425
Gunawardena S, Her LS, Brusch RG, Laymon RA, Niesman IR, Gordesky-Gold B, Sintasath L, Bonini NM, Goldstein LS (2003) Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila. Neuron 40:25–40
Hajnoczky G, Csordas G, Madesh M, Pacher P (2000) Control of apoptosis by IP(3) and ryanodine receptor driven calcium signals. Cell Calcium 28:349–363
Hamada K, Terauchi A, Mikoshiba K (2003) Three-dimensional rearrangements within inositol 1,4,5-trisphosphate receptor by calcium. J Biol Chem 278:52881–52889
Haun S, Sun L, Hubrack S, Yule D, Machaca K (2012) Phosphorylation of the rat Ins(1,4,5)P3 receptor at T930 within the coupling domain decreases its affinity to Ins(1,4,5)P3. Channels (Austin) 6:379–384
Hetz C, Russelakis-Carneiro M, Maundrell K, Castilla J, Soto C (2003) Caspase 12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein. EMBO J 22:5435–5445
Hetz C, Russelakis-Carneiro M, Walchli S, Carboni S, Vial-Knecht E, Maundrell K, Castella J, Soto C (2005) The disulfide isomerase Grp58 is a protective factor against prion neurotoxicity. J Neurosci 25:2793–2802
Higo T, Hattori M, Nakamura T, Natsume T, Michikawa T, Mikoshiba K (2005) Subtypespecific and ER lumenal environment-dependent regulation of inositol 1,4,5-trisphosphate receptor type-1 by ERp44. Cell 120:85–98
Higo T, Hamada K, Hisatsune C, Nukina N, Hashikawa T, Hattori M, Nakamura T, Mikoshiba K (2010) Mechanism of ER stress-induced brain damage by IP3 receptor. Neuron 68:865–878
Ito E, Oka K, Etcheberrigaray R, Nelson TJ, McPhie DL, Tofel-Grehl B, Gibson GE, Alkon DL (1994) Internal Ca2+ mobilization is altered in fibroblasts from patients with Alzheimer disease. Proc Natl Acad Sci U S A 91:534–538
Ito J, Yoon SY, Lee B, Vanderheyden V, Vermassen E, Wojcikiewicz R, Alfandari D, De Smedt H, Parys JB, Fissore RA (2008) Inositol 1,4,5-trisphosphate receptor 1, a widespread Ca2+ channel, is a novel substrate of polo-like kinase 1 in eggs. Dev Biol 320:402–413
Iwai M, Tateishi Y, Hattori M, Mizutani A, Nakamura T, Futatsugi A, Inoue T, Furuichi T, Michikawa T, Mikoshiba K (2005) Molecular cloning of mouse type 2 and type 3 inositol 1,4,5-trisphosphate receptors and identification of a novel type 2 receptor splice variant. J Biol Chem 280:10305–10317
Iwai M, Michikawa T, Bosanac I, Ikura M, Mikoshiba K (2007) Molecular basis of the isoform-specific ligand-binding affinity of inositol 1,4,5-trisphosphate receptors. J Biol Chem 282:12755–12764
Kaftan EJ, Ehrlich BE, Watras J (1997) Inositol 1,4,5-trisphosphate (InsP3) and calcium interact to increase the dynamic range of InsP3 receptor-dependent calciumsignaling. J Gen Physiol 110:529–538
Kaja S, Duncan RS, Longoria S, Hilgenberg JD, Payne J, Desai NM, Parikh R, Burroughs L, Gregg V, Goad I, Koulen P (2011) novel mechanism of increased ca2 release following oxidative stress in neuronal cells involves type 2 inositol-1,4,5-trisphosphate receptors. Neuroscience 175:281–291
Kasri NN, Holmes AM, Bultynck G, Parys JB, Bootman MD, Rietdorf K, Missiaen L, McDonald F, De Smedt H, Conway SJ, Holmes AB, Berridge MJ, Roderick HL (2004a) Regulation of InsP3 receptor activity by neuronal Ca2 + -binding proteins. EMBO J 23:312–321
Kasri NN, Bultynck G, Smyth J, Szlufcik K, Parys JB, Callewaert G, Missiaen L, Fissore RA, Mikoshiba K, de Smedt H (2004b) The N-terminal Ca2+ independent calmodulin-binding site on the inositol 1,4,5-trisphosphate receptor is responsible for calmodulin inhibition, even though this inhibition requires Ca2+. Mol Pharmacol 66:276–284
Kasri NN, Torok K, Galione A, Garnham C, Callewaert G, Missiaen L, Parys JB, De Smedt H (2006) Endogenously bound calmodulin is essential for the function of the inositol 1,4,5-trisphosphate receptor. J Biol Chem 281:8332–8338
Khan MT, Wagner L 2nd, Yule DI, Bhanumathy C, Joseph SK (2006) Akt kinase phosphorylation of inositol 1,4,5-trisphosphate receptors. J Biol Chem 281:3731–3737
Khan SA, Rossi AM, Riley AM, Potter BV, Taylor CW (2013) Subtype-selective regulation of IP3 receptors by thimerosal via cysteine residues within the IP3-binding core and suppressor domain. Biochem J 451:177–184
Li H, Li SH, Yu ZX, Shelbourne P, Li XJ (2001) Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington’s disease mice. J Neurosci 21:8473–8481
Li C, Chan J, Haeseleer F, Mikoshiba K, Palczewski K, Ikura M, Ames JB (2009) Structural insights into Ca2 + -dependent regulation of inositol 1,4,5-trisphosphate receptors by CaBP1. J Biol Chem 284:2472–2481
Li C, Enomoto M, Rossi AM, Seo MD, Rahman T, Stathopulos PB, Taylor CW, Ikura M, Ames JB (2013) CaBP1, a neuronal Ca2+ sensor protein, inhibits inositol trisphosphate receptors by clamping intersubunit interactions. Proc Natl Acad Sci U S A 110:8507–8512
Lin C, Widjaja J, Joseph SK (2000) The interaction of calmodulin with alternatively spliced isoforms of the type-I inositol trisphosphate receptor. J Biol Chem 275:2305–2311
Lino M (1990) Biphasic Ca2+ dependence of inositol 1,4,5-trisphosphate-induced Ca release in smooth muscle cells of the Guinea pig Taenia caeci. J Gen Physiol 95:1103–1122
Lino L (1991) Effects of adenine nucleotides on inositol 1,4,5-trisphosphate-induced calcium release in vascular smooth muscle cells. J Gen Physiol 98:681–698
Ludtke SJ, Tran TP, Ngo QT, Moiseenkova-Bell VY, Chiu W, Serysheva II (2011) Flexible architecture of IP3R1 by Cryo-EM. Structure 19:1192–1199
Maes K, Missiaen L, De Smet P, Vanlingen S, Callewaert G, Parys JB, De Smedt H (2000) Differential modulation of inositol 1,4,5-trisphosphate receptor type-1 and type-3by ATP. Cell Calcium 27:257–267
Mak DO, McBride S, Foskett JK (1998) Inositol 1,4,5-trisphosphate (correction of trisphosphate) activation of inositol trisphosphate (correction of triphosphate) receptor Ca2+ channel by ligand tuning of Ca2+ inhibition. Proc Natl Acad Sci U S A 95:15821–15825
Mak DO, McBride S, Foskett JK (2001) Regulation by Ca2+ and inositol 1,4,5- trisphosphate (InsP3) of single recombinant type 3 InsP3 receptor channels. Ca2+ activation uniquely distinguishes types 1 and 3 InsP3 receptors. J Gen Physiol 117:435–446
Mak DO, McBride SM, Foskett JK (2003a) Spontaneous channel activity of the inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R). Application of allosteric modeling to calcium and InsP3 regulation of InsP3R single-channel gating. J Gen Physiol 122:583–603
Mak DO, McBride SM, Petrenko NB, Foskett JK (2003b) Novel regulation of calcium inhibition of the inositol 1,4,5-trisphosphate receptor calcium-release channel. J Gen Physiol 122:569–581
Malathi K, Kohyama S, Ho M, Soghoian D, Li X, Silane M, Berenstein A, Jayaraman T (2003) Inositol 1,4,5-trisphosphate receptor (type 1) phosphorylation and modulation by Cdc2. J Cell Biochem 90:1186–1196
Malathi K, Li X, Krizanova O, Ondrias K, Sperber K, Ablamunits V, Jayaraman T (2005) Cdc2/cyclin B1 interacts with and modulates inositol 1,4,5-trisphosphate receptor (type 1) functions. J Immunol 175:6205–6210
Manning BD, Cantley LC (2007) AKT/PKB signaling: navigating downstream. Cell 129:1261–1274
Mansuy IM (2003) Calcineurine in memory and bidirectional plasticity. Biochem Biophys Res Commun 311:1195–1208
Maranto AR (1994) Primary structure, ligand binding, and localization of the human type 3 inositol 1,4,5-trisphosphate receptor expressed in intestinal epithelium. J Biol Chem 269:1222–1230
Marchant JS, Taylor CW (1997) Cooperative activation of IP3 receptors by sequential binding of IP3 and Ca2+ safeguards against spontaneous activity. Curr Biol 7:510–518
Marchi S, Rimessi A, Giorgi C, Baldini C, Ferroni L, Rizzuto R, Pinton P (2008) Akt kinase reducing endoplasmic reticulum Ca2+ release protects cells from Ca2 + -dependent apoptotic stimuli. Biochem Biophys Res Commun 375:501–505
Michikawa T, Hamanaka H, Otsu H, Yamamoto A, Miyawaki A, Furuichi T, Tashiro Y, Mikoshiba K (1994) Transmembrane topology and sites of N-glycosylation of inositol 1,4,5-trisphosphate receptor. J Biol Chem 269:9184–9189
Michikawa T, Hirota J, Kawano S, Hiraoka M, Yamada M, Furuichi T, Mignery GA, Sudhof TC (1999) The ligand binding site and transduction mechanism in the inositol 1,4,5-triphosphate receptor. EMBO J 9:3893–3898
Mignery GA, Sudhof TC (1990) The ligand binding site and transduction mechanism in the inositol 1,4,5-triphosphate receptor. EMBO J 9(12)3893–3898
Mikoshiba K (2007a) IP3 receptor/Ca2+ channel: from discovery to new signaling concepts. J Neurochem 102:1426–1446
Mikoshiba K (2007b) The IP3 receptor/Ca2+ channel and its cellular function. Biochem Soc Symp(74)9–22
Missiaen L, Taylor CW, Berridge MJ (1991) Spontaneous calcium release from inositol trisphosphate-sensitive calcium stores. Nature 352:241–244
Missiaen L, De Smedt H, Droogmans G, Casteels R (1992a) Ca2+ release induced by inositol 1,4,5-trisphosphate is a steady-state phenomenon controlled by luminal Ca2+ in permeabilized cells. Nature 357:599–602
Missiaen L, De Smedt H, Droogmans G, Casteels R (1992b) Luminal Ca2+ controls the activation of the inositol 1,4,5-trisphosphate receptor by cytosolic Ca2+. J Biol Chem 267:22961–22966
Missiaen L, De Smedt H, Parys JB, Sienaert I, Valingen S, Casteels R (1996a) Threshold for inositol 1,4,5-trisphosphate action. J Biol Chem 271:12287–12293
Missiaen L, De Smedt H, Parys JB, Sienaert I, Vanlingen S, Casteels R (1996b) Effects of luminal Ca2+ on inositol trisphosphate-induced Ca2+ release: facts or artifacts. Cell Calcium 19:91–93
Missiaen L, Parys JB, Sienaert I, Maes K, Kunzelmann K, Takahashi M, Tanzawa K, De Smedt H (1998) Functional properties of the type-3 InsP3 receptor in 16 HBE140-bronchial mucosal cells. J Biol Chem 273:8983–8986
Missiaen L, Parys JB, Weidema AF, Sipma H, Vanlingen S, De Smet P, Callewaert G, De Smedt H (1999) The bell-shaped Ca2+ dependence of the inositol 1,4,5-trisphosphate-induced Ca2+ release is modulated by Ca2+/calmodulin. J Biol Chem 274:13748–13751
Missiaen L, DeSmedt H, Bultynck G, Vanlingen S, Desmet P, Callewaert G, Parys JB (2000) Calmodulin increases the sensitivity of type-3 inositol 1,4,5-trisphosphate receptors to Ca2+ inhibition in human bronchial mucosal cells. Mol Pharmacol 57:564–567
Miyakawa T, Maeda A, Yamazawa T, Hirose K, Kurosaki T, Iino M (1999) Encoding of Ca2+ signals by differential expression of IP3 receptor subtypes. EMBO J 18:1303–1308
Miyakawa T, Mizushima A, Hirose K, Yamazawa T, Bezprozvanny I, Kurosaki T, Iino M (2001) Ca2 + -sensor region of IP3 receptor controls intracellular Ca2+ signaling. EMBO J 20:1674–1680
Miyawaki A, Furuichi T, Ryou Y, Yoshikawa S, Nakagawa T, Saitoh T, Mikoshiba K (1991) Structure–function relationships of the mouse inositol 1,4,5-trisphosphate receptor. Proc Natl Acad Sci U S A 88:4911–4915
Monkawa T, Miyawaki A, Sugiyama T, Yoneshima H, Yamamoto-Hino M, Furuichi T, Saruta T, Hasegawa M, Mikoshiba K (1995) Heterotetrameric complex formation of inositol 1,4,5-trisphosphate receptor subunits. J Biol Chem 270:14700–14704
Mukherjee A, Morales-Scheihing D, Gonzalez-Romero D, Green K, Taglialatela G, Soto C (2010) Calcineurin inhibition at clinical phase of prion disease reduces neurodegeneration, increased behavioral alterations and increased animal survival. PLoS Pathog 6(10):e1001138
Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, Yuan J (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β. Nature 403:98–103
Nelson O, Tu H, Lei T, Bentahir M, de Strooper B, Bezprozvanny I (2007) Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1. J Clin Invest 117:1230–1239
Onoue H, Tanaka H, Tanaka K, Doira N, Ito Y (2000) Heterooligomer of type 1 and type 2 inositol 1,4,5-trisphosphate receptor expressed in rat liver membrane fraction exists as tetrameric complex. Biochem Biophys Res Commun 267:928–933
Park HS, Betzenhauser MJ, Won JH, Chen J, Yule DI (2008) The type-2 inositol (1,4,5)- trisphosphate (InsP3) receptor determines the sensitivity of InsP3-induced Ca2+ release to ATP in pancreatic acinar cells. J Biol Chem 283:26081–26088
Parys JB, Missiaen L, De Smedt H, Droogmans G, Casteels R (1993a) Bell-shaped activation of inositol-1,4,5-trisphosphate-induced Ca2+ release by thimerosal in permeabilized A7r5 smooth-muscle cells. Pflugers Arch 424:516–522
Parys JB, Missiaen L, De Smedt H, Casteels R (1993b) Loading dependence of inositol 1,4,5-trisphosphate-induced Ca2+ release in the clonal cell line A7r5. Implications for themechanismof quantal Ca2+ release. J Biol Chem 268:25206–25212
Patel S, Joseph SK, Thomas AP (1999) Molecular properties of inositol 1,4,5-trisphosphate receptors. Cell Calcium 25:247–264
Patterson D, Boehning SHS (2004) Inositol 1,4,5-trisphosphate receptors as signal integrators. Annu Rev Biochem 73:437–465
Reese LC, Zhang WR, Dineley KT, Kayed R, Taglialatela G (2008) Selective induction of calcineurin activity and signaling by oligomeric amyloid beta. Aging Cell 7:824–835
Regimbald-Dumas Y, Arguin G, Fregeau MO, Guillemette G (2007) cAMP-dependent protein kinase enhances inositol 1,4,5-trisphosphate-induced Ca2+ release in AR4-2 J cells. J Cell Biochem 101:609–618
Rossi AM, Taylor CW (2004) Ca2+ regulation of inositol 1,4,5-trisphosphate receptors: can Ca2+ function without calmodulin? Mol Pharmacol 66:199–203
Roy S, Zhang B, Lee VM, Trojanowski JQ (2005) Axonal transport defects: a common theme in neurodegenerative diseases. Acta Neuropathol 109:5–13
Schug ZT, Joseph SK (2006) The role of the S4–S5 linker and C-terminal tail in inositol 1,4,5-trisphosphate receptor function. J Biol Chem 281:24431–24440
Seo MD, Velamakanni S, Ishiyama N, Stathopulos PB, Rossi AM, Khan SA, Dale P, Li C, Ames JB, Ikura M, Taylor CW (2012) Structural and functional conservation of key domains in InsP3 and ryanodine receptors. Nature 483:108–112
Shinohara T, Michikawa T, Enomoto M, Goto J, Iwai M, Matsu-ura T, Yamazaki H, Miyamoto A, Suzuki A, Mikoshiba K (2011) Mechanistic basis of bellshaped dependence of inositol 1,4,5-trisphosphate receptor gating on cytosolic calcium. Proc Natl Acad Sci U S A 108:15486–15491
Sienaert I, Missiaen L, De Smedt H, Parys JB, Sipma H, Casteels R (1997) Molecular and functional evidence for multiple Ca2 + -binding domains in the type-1 inositol 1,4,5-trisphosphate receptor. J Biol Chem 272:25899–25906
Sienaert I, Huyghe S, Parys JB, Malfait M, Kunzelmann K, De Smedt H, Verleden GM, Missiaen L (1998) ATP-induced Ca2+ signals in bronchial epithelial cells. Pflugers Arch 436:40–48
Soulsby MD, Wojcikiewicz RJ (2005) The type III inositol 1,4,5-trisphosphate receptor is phosphorylated by cAMP-dependent protein kinase at three sites. Biochem J 392:493–497
Soulsby MD, Wojcikiewicz RJ (2007) Calcium mobilization via type III inositol 1,4,5-trisphosphate receptors is not altered by PKA-mediated phosphorylation of serines 916, 934, and 1832. Cell Calcium 42:261–270
Stokin GB, Lillo C, Falzone TL (2005) Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease. Science 307(2005):1282–1288
Stutzmann GE (2007) The pathogenesis of Alzheimers disease is it a lifelong “calciumopathy”. Neuroscientist 13:546–559
Stutzmann GE, Caccamo A, LaFerla FM, Parker I (2004) Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer's-linked mutation in presenilin 1 results in exaggerated Ca2+ signals and altered membrane excitability. J Neurosci Off J Soc Neurosci 24:508–513
Sudhof TC, Newton CL, Archer BT 3rd, Ushkaryov YA, Mignery GA (1991) Structure of a novel InsP3 receptor. EMBO J 10:3199–3206
Sun Y, Taylor CW (2008) A calmodulin antagonist reveals a calmodulin-independent interdomain interaction essential for activation of inositol 1,4,5-trisphosphate receptors. Biochem J 416:243–253
Sun L, Haun S, Jones RC, Edmondson RD, Machaca K (2009) Kinase-dependent regulation of inositol 1,4,5-trisphosphate-dependent Ca2+ release during oocyte maturation. J Biol Chem 284:20184–20196
Sun Y, Rossi AM, Rahman T, Taylor CW (2013) Activation of IP3 receptors requires an endogenous 1-8-14 calmodulin-binding motif. Biochem J 449:39–49
Swann K (1991) Thimerosal causes calcium oscillations and sensitizes calcium-induced calcium release in unfertilized hamster eggs. FEBS Lett 278:175–178
Szabadkai G, Bianchi K, Varnai P et al (2006) Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J Cell Biol 175:901–911
Szado T, Vanderheyden V, Parys JB, De Smedt H, Rietdorf K, Kotelevets L, Chastre E, Khan F, Landegren U, Soderberg O, Bootman MD, Roderick HL (2008) Phosphorylation of inositol 1,4,5-trisphosphate receptors by protein kinase B/Akt inhibits Ca2+ release and apoptosis. Proc Natl Acad Sci U S A 105:2427–2432
Taglialatela G, Hogan D, Zhang WR, Dineley KT (2008) Intermediate- and long-term memory deficits in Tg2576 mice are reversed with acute calcineurin inhibition. Behav Brain Res 200(1):95–99
Tang TS, Tu H, Chan EY, Maximov A, Wang Z, Wellington CL, Hayden MR, Bezprozvanny I (2003) Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1. Neuron 39:227–239
Tanimura A, Turner RJ (1996) Calcium release in HSY cells conforms to a steady-state mechanism involving regulation of the inositol 1,4,5-trisphosphate receptor Ca2 + channel by luminal [Ca2+]. J Cell Biol 132:607–616
Tardif KD, Waris G, Siddiqui A (2005) Hepatitis C virus, ER stress, and oxidative stress. Trends Microbiol 13:159–163
Taylor CW, Tovey SC (2010) IP3 receptors: toward understanding their activation. Cold Spring Harb Perspect Biol 2:a004010
Tu H, Nosyreva E, Miyakawa T, Wang Z, Mizushima A, Iino M, Bezprozvanny I (2003) Functional and biochemical analysis of the type-1 inositol 1,4,5-trisphosphate receptor calcium sensor. Biophys J 85:290–299
Tu H, Wang Z, Bezprozvanny I (2005a) Modulation of mammalian inositol 1,4,5-trisphosphate receptor isoforms by calcium: a role of calcium sensor region. Biophys J 88:1056–1069
Tu H, Wang Z, Nosyreva E, De Smedt H, Bezprozvanny I (2005b) Functional characterization of mammalian inositol 1,4,5-trisphosphate receptor isoforms. Biophys J 88:1046–1055
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 126:981–993
Uchida K, Miyauchi H, Furuichi T, Michikawa T, Mikoshiba K (2003) Critical regions for activation gating of the inositol 1,4,5-trisphosphate receptor. J Biol Chem 278:16551–16560
Vais H, Foskett JK, Ullah G, Pearson JE, Daniel Mak DO (2012) Permeant calcium ion feed-through regulation of single inositol 1,4,5-trisphosphate receptor channel gating. J Gen Physiol 140:697–716
Vanderheyden V, Devogelaere B, Missiaen L, De Smedt H, Bultynck G, Parys JB (2009a) Regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release by reversible phosphorylation and dephosphorylation. Biochim Biophys Acta 1793:959–970
Vanderheyden V, Wakai T, Bultynck G, De Smedt H, Parys JB, Fissore RA (2009b) Regulation of inositol 1,4,5-trisphosphate receptor type 1 function during oocyte maturation by MPM-2 phosphorylation. Cell Calcium 46:56–64
Vanlingen S, Sipma H, Missiaen L, De Smedt H, De Smet P, Casteels R, Parys JB (1999) Modulation of type 1, 2 and 3 inositol 1,4,5-trisphosphate receptors by cyclic ADPribose and thimerosal. Cell Calcium 25:107–114
Vanlingen S, Sipma H, De Smet P, Callewaert G, Missiaen L, De Smedt H, Parys JB (2000) Ca2+ and calmodulin differentially modulate myo-inositol 1,4,5-trisphosphate (IP3)-binding to the recombinant ligand-binding domains of the various IP3 receptor isoforms. Biochem J 346:275–280
Vanlingen S, Sipma H, De Smet P, Callewaert G, Missiaen L, De Smedt H, Parys JB (2001) Modulation of inositol 1,4,5-trisphosphate binding to the various inositol 1,4,5-trisphosphate receptor isoforms by thimerosal and cyclic ADP-ribose. Biochem Pharmacol 61:803–809
Wagner LE 2nd, Li WH, Yule DI (2003) Phosphorylation of type-1 inositol 1,4,5-trisphosphate receptors by cyclic nucleotide-dependent protein kinases: a mutational analysis of the functionally important sites in the S2+ and S2− splice variants. J Biol Chem 278:45811–45817
Wagner LE 2nd, Li WH, Joseph SK, Yule DI (2004) Functional consequences of phosphomimetic mutations at key cAMP-dependent protein kinase phosphorylation sites in the type-1 inositol 1,4,5-trisphosphate receptor. J Biol Chem 279:46242–46252
Wagner LE 2nd, Betzenhauser MJ, Yule DI (2006) ATP binding to a unique site in the type-1 S2− inositol 1,4,5-trisphosphate receptor defines susceptibility to phosphorylation by protein kinase A. J Biol Chem 281:17410–17419
Wagner LE 2nd, Joseph SK, Yule DI (2008) Regulation of single inositol 1,4,5-trisphosphate receptor channel activity by protein kinase A phosphorylation. J Physiol 586:3577–3596
Wojcikiewicz RJ, Luo SG (1998) Phosphorylation of inositol 1,4,5-trisphosphate receptors by cAMP-dependent protein kinase. Type I, II, and III receptors are differentially susceptible to phosphorylation and are phosphorylated in intact cells. J Biol Chem 273:5670–5677
Yamada M, Miyawaki A, Saito K, Nakajima T, Yamamoto-Hino M, Ryo Y, Furuichi T, Mikoshiba K (1995) The calmodulin-binding domain in the mouse type-1 inositol 1,4,5-trisphosphate receptor. Biochem J 308:83–88
Yamasaki-Mann M, Parker I (2011) Enhanced ER Ca2+ store filling by overexpression of SERCA2b promotes IP3-evoked puffs. Cell Calcium 50:36–41
Yamasaki-Mann M, Demuro A, Parker I (2010) Modulation of endoplasmic reticulum Ca2+ store filling by cyclic ADP-ribose promotes inositol trisphosphate (IP3)-evoked Ca2+ signals. J Biol Chem 285:25053–25061
Yang LH, Bai GR, Huang XY, Sun FZ (2006) ERK binds, phosphorylates InsP3 type 1 receptor and regulates intracellular calcium dynamics in DT40 cells. Biochem Biophys Res Commun 349:1339–1344
Yoshikawa F, Morita M, Monkawa T, Michikawa T, Furuichi T, Mikoshiba K (1996) Mutational analysis of the ligand binding site of the inositol 1,4,5-trisphosphate receptor. J Biol Chem 271:18277–18284
Yoshikawa F, Iwasaki H, Michikawa T, Furuichi T, Mikoshiba K (1999) Trypsinized cerebellar inositol 1,4,5-trisphosphate receptor. Structural and functional coupling of cleaved ligand binding and channel domains. J Biol Chem 274:316–327
Yule DI, Betzenhauser MJ, Joseph SK (2010) Linking structure to function: recent lessons from inositol 1,4,5-trisphosphate receptor mutagenesis. Cell Calcium 47:469–479
Zhang H, Sun S, Herreman A, De Strooper B, Bezprozvanny I (2010) Role of presenilins in neuronal calcium homeostasis. J Neurosci Off J Soc Neurosci 30:8566–8580
Acknowledgments
This work was supported by 948 projects (2014-S9) and the Program for Cheung Kong Scholars and Innovative Research Team in University of China (No. IRT0866).
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Shah, S.Z.A., Zhao, D., Khan, S.H. et al. Regulatory Mechanisms of Endoplasmic Reticulum Resident IP3 Receptors. J Mol Neurosci 56, 938–948 (2015). https://doi.org/10.1007/s12031-015-0551-4
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DOI: https://doi.org/10.1007/s12031-015-0551-4