title: Inositol 1,4,5-trisphosphate receptors and their protein partners as signalling hubs.
abstract: Inositol 1,4,5-trisphosphate receptors (IP3 Rs) are expressed in nearly all animal cells, where they mediate the release of Ca(2+) from intracellular stores. The complex spatial and temporal organization of the ensuing intracellular Ca(2+) signals allows selective regulation of diverse physiological responses. Interactions of IP3 Rs with other proteins contribute to the specificity and speed of Ca(2+) signalling pathways, and to their capacity to integrate information from other signalling pathways. In this review, we provide a comprehensive survey of the proteins proposed to interact with IP3 Rs and the functional effects that these interactions produce. Interacting proteins can determine the activity of IP3 Rs, facilitate their regulation by multiple signalling pathways and direct the Ca(2+) that they release to specific targets. We suggest that IP3 Rs function as signalling hubs through which diverse inputs are processed and then emerge as cytosolic Ca(2+) signals.
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, UK.
authors.forename: David L
authors.initials: DL
authors.lastname: Prole
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, UK.
authors.forename: Colin W
authors.initials: CW
authors.lastname: Taylor
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D008565:Membrane Proteins; D015544:Inositol 1,4,5-Trisphosphate
references.citation: J Biol Chem. 2003 Dec 26;278(52):52881-9
references.pmid: 14593123
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13293-8
references.pmid: 21784978
references.citation: Cell Calcium. 2011 Aug;50(2):175-83
references.pmid: 21176957
references.citation: Biochem Biophys Res Commun. 2006 Oct 6;348(4):1319-27
references.pmid: 16925983
references.citation: Nat Methods. 2015 Jan;12(1):79-84
references.pmid: 25402006
references.citation: Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1186-91
references.pmid: 24395794
references.citation: Mol Cell Neurosci. 2003 Feb;22(2):271-83
references.pmid: 12676536
references.citation: Trends Plant Sci. 2008 Sep;13(9):506-14
references.pmid: 18703378
references.citation: J Cell Biol. 2008 Oct 20;183(2):297-311
references.pmid: 18936250
references.citation: J Biol Chem. 1993 Mar 25;268(9):6477-86
references.pmid: 8384211
references.citation: Mol Cell Proteomics. 2006 Dec;5(12 ):2211-27
references.pmid: 16959763
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2328-32
references.pmid: 14983009
references.citation: J Biol Chem. 2006 Jul 28;281(30):20825-33
references.pmid: 16723353
references.citation: Nature. 2012 Apr 08;485(7396):128-32
references.pmid: 22495310
references.citation: Neuron. 1994 Feb;12(2):327-42
references.pmid: 8110462
references.citation: Nat Cell Biol. 2005 Oct;7(10):1021-8
references.pmid: 16179951
references.citation: Biochem Biophys Res Commun. 2004 Jan 16;313(3):654-65
references.pmid: 14697242
references.citation: Proc Natl Acad Sci U S A. 2013 May 21;110(21):8507-12
references.pmid: 23650371
references.citation: J Biol Chem. 2005 Oct 14;280(41):34530-7
references.pmid: 16103111
references.citation: Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20593-8
references.pmid: 24297914
references.citation: Science. 2005 Sep 30;309(5744):2232-4
references.pmid: 16195467
references.citation: Biochem Biophys Res Commun. 2015 Apr 24;460(1):72-81
references.pmid: 25998735
references.citation: Nature. 2002 Dec 12;420(6916):696-700
references.pmid: 12442173
references.citation: Cold Spring Harb Perspect Biol. 2010 Dec;2(12):a004010
references.pmid: 20980441
references.citation: PLoS One. 2013 Jul 23;8(7):e69473
references.pmid: 23936024
references.citation: J Biol Chem. 2004 Apr 16;279(16):16311-6
references.pmid: 14761954
references.citation: Cell Motil Cytoskeleton. 2002 Dec;53(4):293-316
references.pmid: 12378540
references.citation: J Biol Chem. 2003 Aug 29;278(35):33492-500
references.pmid: 12766172
references.citation: J Biol Chem. 2007 Jul 13;282(28):20104-15
references.pmid: 17502376
references.citation: Biochem J. 2011 Jun 1;436(2):231-9
references.pmid: 21568942
references.citation: J Biol Chem. 2006 Feb 10;281(6):3731-7
references.pmid: 16332683
references.citation: J Biol Chem. 1991 Jan 15;266(2):1109-16
references.pmid: 1845986
references.citation: Cell Death Differ. 2013 Dec;20(12):1631-43
references.pmid: 23811847
references.citation: Semin Cell Dev Biol. 2012 Apr;23(2):172-80
references.pmid: 21925615
references.citation: Annu Rev Physiol. 2010;72:463-93
references.pmid: 20148685
references.citation: Neuron. 2010 Dec 9;68(5):865-78
references.pmid: 21145001
references.citation: PLoS One. 2011;6(10):e26218
references.pmid: 22022573
references.citation: Nat Chem Biol. 2014 Sep;10(9):716-22
references.pmid: 25038791
references.citation: Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2232-5
references.pmid: 1848697
references.citation: Nucleic Acids Res. 2015 Jan;43(Database issue):D470-8
references.pmid: 25428363
references.citation: J Cell Biochem. 2011 Feb;112(2):723-33
references.pmid: 21268094
references.citation: Circulation. 2013 Oct 1;128(14):1555-65
references.pmid: 23983249
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1357-9
references.pmid: 15677321
references.citation: J Biol Chem. 2010 Mar 12;285(11):8045-53
references.pmid: 20022948
references.citation: Science. 2014 Sep 19;345(6203):1512-5
references.pmid: 25237103
references.citation: Curr Biol. 1997 Jul 1;7(7):510-8
references.pmid: 9210378
references.citation: BMC Biochem. 2015 Apr 30;16:11
references.pmid: 25924612
references.citation: FEBS Lett. 2000 Jan 21;466(1):29-34
references.pmid: 10648806
references.citation: Biochim Biophys Acta. 2009 Jun;1793(6):959-70
references.pmid: 19133301
references.citation: Cell Rep. 2015 Jul 7;12(1):79-89
references.pmid: 26119739
references.citation: FEBS Open Bio. 2012 Sep 04;2:255-9
references.pmid: 23650607
references.citation: J Biol Chem. 1996 Jul 12;271(28):16652-5
references.pmid: 8663308
references.citation: Neuron. 1998 Oct;21(4):717-26
references.pmid: 9808459
references.citation: Nature. 1986 Sep 4-10;323(6083):68-71
references.pmid: 3018586
references.citation: FEBS J. 2011 May;278(10):1757-68
references.pmid: 21418524
references.citation: Pflugers Arch. 2011 Oct;462(4):599-610
references.pmid: 21811790
references.citation: J Immunol. 2005 Nov 1;175(9):6205-10
references.pmid: 16237118
references.citation: Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3168-73
references.pmid: 11248050
references.citation: Cell Calcium. 2002 Nov-Dec;32(5-6):235-49
references.pmid: 12543086
references.citation: Annu Rev Pharmacol Toxicol. 2013;53:187-210
references.pmid: 23043438
references.citation: Biochim Biophys Acta. 2014 Oct;1843(10):2195-204
references.pmid: 24518248
references.citation: J Membr Biol. 1984;81(3):241-53
references.pmid: 6334162
references.citation: Nature. 1985 Jul 25-31;316(6026):347-9
references.pmid: 2410794
references.citation: Biochim Biophys Acta. 2013 Nov;1833(11):2542-59
references.pmid: 23770047
references.citation: Cell Calcium. 2009 Jul;46(1):56-64
references.pmid: 19482353
references.citation: Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16478-83
references.pmid: 25368151
references.citation: Biochem J. 1999 Apr 15;339 ( Pt 2):453-61
references.pmid: 10191279
references.citation: Science. 1996 Jun 7;272(5267):1492-4
references.pmid: 8633244
references.citation: J Biol Chem. 2009 Apr 17;284(16):10433-45
references.pmid: 19240031
references.citation: Tumour Biol. 2005 Jul-Aug;26(4):207-12
references.pmid: 16006774
references.citation: PLoS One. 2013;8(3):e60609
references.pmid: 23555994
references.citation: Physiol Rev. 2007 Apr;87(2):593-658
references.pmid: 17429043
references.citation: J Biol Chem. 2004 Jan 23;279(4):2885-93
references.pmid: 14593108
references.citation: FEBS Lett. 1993 Jun 1;323(3):229-32
references.pmid: 8388808
references.citation: Oncogene. 2004 Apr 8;23(15):2617-29
references.pmid: 14968112
references.citation: Cell. 2012 Aug 31;150(5):1068-81
references.pmid: 22939629
references.citation: Am J Physiol Cell Physiol. 2004 Dec;287(6):C1667-78
references.pmid: 15329338
references.citation: J Cell Biol. 2000 Sep 4;150(5):1101-12
references.pmid: 10973998
references.citation: Sci Signal. 2010 Mar 23;3(114):ra22
references.pmid: 20332427
references.citation: Physiol Rev. 2005 Apr;85(2):757-810
references.pmid: 15788710
references.citation: J Biol Chem. 2005 Feb 25;280(8):6816-22
references.pmid: 15583010
references.citation: Neuron. 2003 Jul 17;39(2):227-39
references.pmid: 12873381
references.citation: Dev Biol. 2008 Aug 15;320(2):402-13
references.pmid: 18621368
references.citation: Cell. 2009 Jul 23;138(2):366-76
references.pmid: 19632184
references.citation: J Biol Chem. 2002 May 3;277(18):15801-6
references.pmid: 11842082
references.citation: Curr Top Membr. 2010;66:273-98
references.pmid: 22353484
references.citation: J Biol Chem. 2007 Jun 1;282(22):16631-43
references.pmid: 17416589
references.citation: Mol Biol Cell. 2009 Aug;20(16):3638-45
references.pmid: 19553469
references.citation: Cell Cycle. 2004 Mar;3(3):252-4
references.pmid: 14726673
references.citation: Cell. 2005 Jan 14;120(1):85-98
references.pmid: 15652484
references.citation: Nature. 1996 Jan 11;379(6561):168-71
references.pmid: 8538767
references.citation: J Cell Biol. 2004 Jul 19;166(2):193-203
references.pmid: 15263017
references.citation: Science. 2009 Nov 27;326(5957):1220-4
references.pmid: 19965465
references.citation: J Biol Chem. 2009 Jan 2;284(1):372-80
references.pmid: 18990696
references.citation: J Mol Endocrinol. 2014 Jun;52(3):333-44
references.pmid: 24711643
references.citation: J Biol Chem. 2003 Mar 21;278(12):10602-12
references.pmid: 12525476
references.citation: J Biol Chem. 1995 Oct 6;270(40):23310-6
references.pmid: 7559486
references.citation: Cold Spring Harb Perspect Biol. 2011 Dec 01;3(12):null
references.pmid: 21791698
references.citation: Biochem Biophys Res Commun. 2011 Apr 8;407(2):438-43
references.pmid: 21420385
references.citation: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7711-6
references.pmid: 12032348
references.citation: Curr Biol. 2002 Jun 4;12(11):951-6
references.pmid: 12062062
references.citation: J Biol Chem. 2004 Mar 26;279(13):12980-7
references.pmid: 14722080
references.citation: Cell. 2003 Sep 19;114(6):777-89
references.pmid: 14505576
references.citation: Nature. 2000 Mar 9;404(6774):197-201
references.pmid: 10724174
references.citation: Neuron. 2002 Apr 11;34(2):209-20
references.pmid: 11970863
references.citation: J Biol Chem. 2004 Jan 2;279(1):547-55
references.pmid: 14570872
references.citation: J Cell Biochem. 2003 Dec 15;90(6):1186-96
references.pmid: 14635192
references.citation: Exp Cell Res. 2004 Apr 15;295(1):102-18
references.pmid: 15051494
references.citation: Am J Physiol Cell Physiol. 2009 Mar;296(3):C403-13
references.pmid: 19052258
references.citation: J Cell Sci. 2010 May 1;123(Pt 9):1449-59
references.pmid: 20375063
references.citation: EMBO J. 2004 Jan 28;23(2):312-21
references.pmid: 14685260
references.citation: J Neurosci. 2003 Jan 15;23(2):403-15
references.pmid: 12533600
references.citation: J Biol Chem. 2001 Jun 15;276(24):21303-10
references.pmid: 11290752
references.citation: J Biol Chem. 2013 Aug 30;288(35):25340-9
references.pmid: 23884412
references.citation: Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5515-20
references.pmid: 25922519
references.citation: Nature. 2009 Apr 2;458(7238):655-9
references.pmid: 19348050
references.citation: J Biol Chem. 1997 May 9;272(19):12454-61
references.pmid: 9139693
references.citation: Mol Pharmacol. 2010 Jul;78(1):69-80
references.pmid: 20395553
references.citation: J Cell Sci. 2012 Nov 15;125(Pt 22):5428-40
references.pmid: 22946050
references.citation: EMBO J. 1998 Sep 15;17 (18):5298-308
references.pmid: 9736609
references.citation: Biochem J. 1999 Aug 15;342 ( Pt 1):153-61
references.pmid: 10432312
references.citation: J Biol Chem. 2003 Dec 12;278(50):49699-706
references.pmid: 14506248
references.citation: Biochim Biophys Acta. 2009 Jun;1793(6):933-40
references.pmid: 19010359
references.citation: Cell Death Differ. 2009 Jul;16(7):1006-17
references.pmid: 19325567
references.citation: J Biol Chem. 2005 Dec 16;280(50):41298-306
references.pmid: 16223735
references.citation: J Cell Biol. 2007 Dec 3;179(5):923-34
references.pmid: 18056410
references.citation: Eur J Neurosci. 2004 Dec;20(11):2929-44
references.pmid: 15579147
references.citation: Nature. 2011 Jun 19;476(7360):341-5
references.pmid: 21685886
references.citation: Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1784-8
references.pmid: 7533300
references.citation: Chem Senses. 2010 Feb;35(2):171-7
references.pmid: 20071408
references.citation: Biophys J. 2014 Aug 19;107(4):834-45
references.pmid: 25140418
references.citation: J Biol Chem. 2011 Jul 8;286(27):24426-33
references.pmid: 21610068
references.citation: J Physiol Sci. 2011 May;61(3):221-9
references.pmid: 21424589
references.citation: Cell. 2014 Nov 20;159(5):1212-26
references.pmid: 25416956
references.citation: Biochem J. 2004 Jan 15;377(Pt 2):299-307
references.pmid: 12968951
references.citation: J Biol Chem. 2011 Jan 7;286(1):830-41
references.pmid: 21051544
references.citation: Mol Cell Proteomics. 2012 May;11(5):60-76
references.pmid: 22586326
references.citation: J Cell Sci. 2006 Jan 1;119(Pt 1):153-61
references.pmid: 16352659
references.citation: PLoS One. 2010 Sep 01;5(9):null
references.pmid: 20824138
references.citation: J Cell Biol. 2005 May 23;169(4):657-67
references.pmid: 15911880
references.citation: J Biol Chem. 2010 Apr 30;285(18):13678-84
references.pmid: 20189983
references.citation: J Biol Chem. 2004 Apr 30;279(18):19375-82
references.pmid: 14982933
references.citation: J Biol Chem. 2009 Oct 16;284(42):29158-69
references.pmid: 19706611
references.citation: J Biol Chem. 1993 Apr 5;268(10):7290-7
references.pmid: 8385102
references.citation: Mol Biol Cell. 2005 Sep;16(9):4034-45
references.pmid: 15975899
references.citation: Nature. 2012 Jan 29;483(7387):108-12
references.pmid: 22286060
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14955-60
references.pmid: 10611319
references.citation: J Biol Chem. 1999 Nov 26;274(48):34433-7
references.pmid: 10567423
references.citation: Sci Signal. 2013 Aug 27;6(290):ra73
references.pmid: 23982204
references.citation: J Gen Physiol. 2010 Sep;136(3):283-91
references.pmid: 20713546
references.citation: J Cell Biol. 2004 Aug 16;166(4):537-48
references.pmid: 15302852
references.citation: FEBS Lett. 2001 Jan 5;487(3):377-83
references.pmid: 11163362
references.citation: Biochem Biophys Res Commun. 2003 Jan 3;300(1):155-60
references.pmid: 12480535
references.citation: J Clin Invest. 2006 Jun;116(6):1668-74
references.pmid: 16691292
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6404-9
references.pmid: 19332787
references.citation: J Biol Chem. 2006 Dec 1;281(48):37111-6
references.pmid: 16990268
references.citation: PLoS Biol. 2005 Dec;3(12):e423
references.pmid: 16292983
references.citation: Curr Biol. 2003 May 13;13(10):872-6
references.pmid: 12747838
references.citation: J Biol Chem. 2003 Oct 3;278(40):38238-46
references.pmid: 12869571
references.citation: Cell. 2010 Jul 23;142(2):270-83
references.pmid: 20655468
references.citation: EMBO J. 2002 Jan 15;21(1-2):83-92
references.pmid: 11782428
references.citation: Endocrinology. 2009 May;150(5):2190-6
references.pmid: 19147678
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2427-32
references.pmid: 18250332
references.citation: Cell Death Differ. 2016 Feb;23 (2):313-22
references.pmid: 26206086
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):491-6
references.pmid: 11149946
references.citation: FEBS Lett. 1998 May 1;427(1):55-8
references.pmid: 9613599
references.citation: J Biol Chem. 2000 Sep 29;275(39):30293-300
references.pmid: 10906121
references.citation: J Biol Chem. 2002 Jan 11;277(2):1340-8
references.pmid: 11694504
references.citation: Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):E3966-75
references.pmid: 25201980
references.citation: Science. 1997 Dec 12;278(5345):1940-3
references.pmid: 9395395
references.citation: J Biol Chem. 2004 Oct 8;279(41):43227-36
references.pmid: 15284241
references.citation: J Biol Chem. 2005 Apr 22;280(16):15912-20
references.pmid: 15710625
references.citation: Sci STKE. 2006 Nov 28;2006(363):re15
references.pmid: 17132820
references.citation: Nature. 2007 Dec 13;450(7172):1001-9
references.pmid: 18075579
references.citation: Sci Signal. 2010 Mar 23;3(114):pe10
references.pmid: 20332425
references.citation: PLoS One. 2012;7(8):e42404
references.pmid: 22876320
references.citation: Biochem J. 1995 May 15;308 ( Pt 1):83-8
references.pmid: 7755592
references.citation: Biochem Biophys Res Commun. 2012 Nov 9;428(1):31-5
references.pmid: 23058917
references.citation: Biochem J. 2003 Jun 1;372(Pt 2):435-41
references.pmid: 12611586
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D358-63
references.pmid: 24234451
references.citation: Cell Physiol Biochem. 2011;27(6):715-26
references.pmid: 21691089
references.citation: Eur J Cancer. 2013 Nov;49(17):3738-51
references.pmid: 23992640
references.citation: Biochim Biophys Acta. 2008 Jun;1783(6):1163-76
references.pmid: 18191041
references.citation: Cell. 1995 Nov 3;83(3):463-72
references.pmid: 8521476
references.citation: J Neurochem. 2007 Sep;102(5):1426-46
references.pmid: 17697045
references.citation: J Cell Biochem. 2008 Jul 1;104(4):1244-53
references.pmid: 18275062
references.citation: J Biol Chem. 2009 Jul 31;284(31):20763-72
references.pmid: 19497848
references.citation: Neuron. 2008 Jun 26;58(6):871-83
references.pmid: 18579078
references.citation: J Cell Biol. 2006 Dec 18;175(6):901-11
references.pmid: 17178908