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. 1991 Nov;10(11):3199–3206. doi: 10.1002/j.1460-2075.1991.tb04882.x

Structure of a novel InsP3 receptor.

T C Südhof 1, C L Newton 1, B T Archer 3rd 1, Y A Ushkaryov 1, G A Mignery 1
PMCID: PMC453043  PMID: 1655411

Abstract

Inositol 1,4,5-trisphosphate (InsP3) constitutes a major intracellular second messenger that transduces many growth factor and neurotransmitter signals. InsP3 causes the release of Ca2+ from intracellular stores by binding to specific receptors that are coupled to Ca2+ channels. One such receptor from cerebellum has previously been extensively characterized. We have now determined the full structure of a second, novel InsP3 receptor which we refer to as type 2 InsP3 receptor as opposed to the cerebellar type 1 InsP3 receptor. The type 2 InsP3 receptor has the same general structural design as the cerebellar type 1 InsP3 receptor with which it shares 69% sequence identity. Expression of the amino-terminal 1078 amino acids of the type 2 receptor demonstrates high affinity binding of InsP3 to the type 2 receptor with a similar specificity but higher affinity than observed for the type 1 receptor. These results demonstrate the presence of several types of InsP3 receptor in brain and raise the possibility that intracellular Ca2+ signaling may involve multiple pathways with different regulatory properties dependent on different InsP3 receptors.

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Selected References

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  1. Berridge M. J. Calcium oscillations. J Biol Chem. 1990 Jun 15;265(17):9583–9586. [PubMed] [Google Scholar]
  2. Berridge M. J., Irvine R. F. Inositol phosphates and cell signalling. Nature. 1989 Sep 21;341(6239):197–205. doi: 10.1038/341197a0. [DOI] [PubMed] [Google Scholar]
  3. Chadwick C. C., Saito A., Fleischer S. Isolation and characterization of the inositol trisphosphate receptor from smooth muscle. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2132–2136. doi: 10.1073/pnas.87.6.2132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. De Camilli P., Takei K., Mignery G. A., Südhof T. C. InsP3 receptor turnaround. Nature. 1990 Apr 5;344(6266):495–495. doi: 10.1038/344495a0. [DOI] [PubMed] [Google Scholar]
  5. Ely J. A., Hunyady L., Baukal A. J., Catt K. J. Inositol 1,3,4,5-tetrakisphosphate stimulates calcium release from bovine adrenal microsomes by a mechanism independent of the inositol 1,4,5-trisphosphate receptor. Biochem J. 1990 Jun 1;268(2):333–338. doi: 10.1042/bj2680333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ferris C. D., Cameron A. M., Bredt D. S., Huganir R. L., Snyder S. H. Inositol 1,4,5-trisphosphate receptor is phosphorylated by cyclic AMP-dependent protein kinase at serines 1755 and 1589. Biochem Biophys Res Commun. 1991 Feb 28;175(1):192–198. doi: 10.1016/s0006-291x(05)81219-7. [DOI] [PubMed] [Google Scholar]
  7. Ferris C. D., Huganir R. L., Bredt D. S., Cameron A. M., Snyder S. H. Inositol trisphosphate receptor: phosphorylation by protein kinase C and calcium calmodulin-dependent protein kinases in reconstituted lipid vesicles. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2232–2235. doi: 10.1073/pnas.88.6.2232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Furuichi T., Yoshikawa S., Miyawaki A., Wada K., Maeda N., Mikoshiba K. Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400. Nature. 1989 Nov 2;342(6245):32–38. doi: 10.1038/342032a0. [DOI] [PubMed] [Google Scholar]
  9. Guillemette G., Balla T., Baukal A. J., Catt K. J. Characterization of inositol 1,4,5-trisphosphate receptors and calcium mobilization in a hepatic plasma membrane fraction. J Biol Chem. 1988 Apr 5;263(10):4541–4548. [PubMed] [Google Scholar]
  10. Harootunian A. T., Kao J. P., Paranjape S., Adams S. R., Potter B. V., Tsien R. Y. Cytosolic Ca2+ oscillations in REF52 fibroblasts: Ca(2+)-stimulated IP3 production or voltage-dependent Ca2+ channels as key positive feedback elements. Cell Calcium. 1991 Feb-Mar;12(2-3):153–164. doi: 10.1016/0143-4160(91)90017-9. [DOI] [PubMed] [Google Scholar]
  11. Irvine R. F. 'Quantal' Ca2+ release and the control of Ca2+ entry by inositol phosphates--a possible mechanism. FEBS Lett. 1990 Apr 9;263(1):5–9. doi: 10.1016/0014-5793(90)80692-c. [DOI] [PubMed] [Google Scholar]
  12. Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. doi: 10.1083/jcb.108.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lechleiter J., Girard S., Clapham D., Peralta E. Subcellular patterns of calcium release determined by G protein-specific residues of muscarinic receptors. Nature. 1991 Apr 11;350(6318):505–508. doi: 10.1038/350505a0. [DOI] [PubMed] [Google Scholar]
  14. Mignery G. A., Newton C. L., Archer B. T., 3rd, Südhof T. C. Structure and expression of the rat inositol 1,4,5-trisphosphate receptor. J Biol Chem. 1990 Jul 25;265(21):12679–12685. [PubMed] [Google Scholar]
  15. Mignery G. A., Südhof T. C., Takei K., De Camilli P. Putative receptor for inositol 1,4,5-trisphosphate similar to ryanodine receptor. Nature. 1989 Nov 9;342(6246):192–195. doi: 10.1038/342192a0. [DOI] [PubMed] [Google Scholar]
  16. Mignery G. A., Südhof T. C. The ligand binding site and transduction mechanism in the inositol-1,4,5-triphosphate receptor. EMBO J. 1990 Dec;9(12):3893–3898. doi: 10.1002/j.1460-2075.1990.tb07609.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Otsu K., Willard H. F., Khanna V. K., Zorzato F., Green N. M., MacLennan D. H. Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum. J Biol Chem. 1990 Aug 15;265(23):13472–13483. [PubMed] [Google Scholar]
  18. Palmer S., Wakelam M. J. The Ins(1,4,5)P3 binding site of bovine adrenocortical microsomes: function and regulation. Biochem J. 1989 Jun 1;260(2):593–596. doi: 10.1042/bj2600593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Penner R., Matthews G., Neher E. Regulation of calcium influx by second messengers in rat mast cells. Nature. 1988 Aug 11;334(6182):499–504. doi: 10.1038/334499a0. [DOI] [PubMed] [Google Scholar]
  20. Perin M. S., Fried V. A., Slaughter C. A., Südhof T. C. The structure of cytochrome b561, a secretory vesicle-specific electron transport protein. EMBO J. 1988 Sep;7(9):2697–2703. doi: 10.1002/j.1460-2075.1988.tb03123.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Perin M. S., Fried V. A., Stone D. K., Xie X. S., Südhof T. C. Structure of the 116-kDa polypeptide of the clathrin-coated vesicle/synaptic vesicle proton pump. J Biol Chem. 1991 Feb 25;266(6):3877–3881. [PubMed] [Google Scholar]
  22. Petersen O. H., Gallacher D. V., Wakui M., Yule D. I., Petersen C. C., Toescu E. C. Receptor-activated cytoplasmic Ca2+ oscillations in pancreatic acinar cells: generation and spreading of Ca2+ signals. Cell Calcium. 1991 Feb-Mar;12(2-3):135–144. doi: 10.1016/0143-4160(91)90015-7. [DOI] [PubMed] [Google Scholar]
  23. Pietri F., Hilly M., Mauger J. P. Calcium mediates the interconversion between two states of the liver inositol 1,4,5-trisphosphate receptor. J Biol Chem. 1990 Oct 15;265(29):17478–17485. [PubMed] [Google Scholar]
  24. Ross C. A., Bredt D., Snyder S. H. Messenger molecules in the cerebellum. Trends Neurosci. 1990 Jun;13(6):216–222. doi: 10.1016/0166-2236(90)90163-5. [DOI] [PubMed] [Google Scholar]
  25. Ross C. A., Meldolesi J., Milner T. A., Satoh T., Supattapone S., Snyder S. H. Inositol 1,4,5-trisphosphate receptor localized to endoplasmic reticulum in cerebellar Purkinje neurons. Nature. 1989 Jun 8;339(6224):468–470. doi: 10.1038/339468a0. [DOI] [PubMed] [Google Scholar]
  26. Rossier M. F., Capponi A. M., Vallotton M. B. The inositol 1,4,5-trisphosphate-binding site in adrenal cortical cells is distinct from the endoplasmic reticulum. J Biol Chem. 1989 Aug 25;264(24):14078–14084. [PubMed] [Google Scholar]
  27. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Shears S. B. Structural and functional interrelationship of the intracellular receptor for inositol (1,4,5) trisphosphate. Cancer Cells. 1991 Mar;3(3):97–99. [PubMed] [Google Scholar]
  29. Streb H., Irvine R. F., Berridge M. J., Schulz I. Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature. 1983 Nov 3;306(5938):67–69. doi: 10.1038/306067a0. [DOI] [PubMed] [Google Scholar]
  30. Südhof T. C., Lottspeich F., Greengard P., Mehl E., Jahn R. A synaptic vesicle protein with a novel cytoplasmic domain and four transmembrane regions. Science. 1987 Nov 20;238(4830):1142–1144. doi: 10.1126/science.3120313. [DOI] [PubMed] [Google Scholar]
  31. Takeshima H., Nishimura S., Matsumoto T., Ishida H., Kangawa K., Minamino N., Matsuo H., Ueda M., Hanaoka M., Hirose T. Primary structure and expression from complementary DNA of skeletal muscle ryanodine receptor. Nature. 1989 Jun 8;339(6224):439–445. doi: 10.1038/339439a0. [DOI] [PubMed] [Google Scholar]
  32. Villa A., Podini P., Clegg D. O., Pozzan T., Meldolesi J. Intracellular Ca2+ stores in chicken Purkinje neurons: differential distribution of the low affinity-high capacity Ca2+ binding protein, calsequestrin, of Ca2+ ATPase and of the ER lumenal protein, Bip. J Cell Biol. 1991 May;113(4):779–791. doi: 10.1083/jcb.113.4.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Woods N. M., Cuthbertson K. S., Cobbold P. H. Repetitive transient rises in cytoplasmic free calcium in hormone-stimulated hepatocytes. Nature. 1986 Feb 13;319(6054):600–602. doi: 10.1038/319600a0. [DOI] [PubMed] [Google Scholar]
  34. Zorzato F., Fujii J., Otsu K., Phillips M., Green N. M., Lai F. A., Meissner G., MacLennan D. H. Molecular cloning of cDNA encoding human and rabbit forms of the Ca2+ release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum. J Biol Chem. 1990 Feb 5;265(4):2244–2256. [PubMed] [Google Scholar]

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