Home LiteratureArticle Details
PMID: 12717445 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of calcium signals in the nucleus by a nucleoplasmic reticulum.

Nature cell biology ·Vol. 5 ·No. 5 ·2003-05-00 ·Pages 440-6

Echevarría W, Leite MF, Guerra MT, Zipfel WR, Nathanson MH

Abstract

Calcium is a second messenger in virtually all cells and tissues. Calcium signals in the nucleus have effects on gene transcription and cell growth that are distinct from those of cytosolic calcium signals; however, it is unknown how nuclear calcium signals are regulated. Here we identify a reticular network of nuclear calcium stores that is continuous with the endoplasmic reticulum and the nuclear envelope. This network expresses inositol 1,4,5-trisphosphate (InsP3) receptors, and the nuclear component of InsP3-mediated calcium signals begins in its locality. Stimulation of these receptors with a little InsP3 results in small calcium signals that are initiated in this region of the nucleus. Localized release of calcium in the nucleus causes nuclear protein kinase C (PKC) to translocate to the region of the nuclear envelope, whereas release of calcium in the cytosol induces translocation of cytosolic PKC to the plasma membrane. Our findings show that the nucleus contains a nucleoplasmic reticulum with the capacity to regulate calcium signals in localized subnuclear regions. The presence of such machinery provides a potential mechanism by which calcium can simultaneously regulate many independent processes in the nucleus.

MeSH Terms
Active Transport, Cell Nucleus/physiology Calcium/metabolism Calcium Channels/metabolism Calcium Signaling/genetics Cell Membrane/metabolism Cell Nucleus Structures/metabolism,ultrastructure Cytosol/metabolism Endoplasmic Reticulum/metabolism,ultrastructure Eukaryotic Cells/cytology,metabolism Humans Inositol 1,4,5-Trisphosphate/metabolism,pharmacology Inositol 1,4,5-Trisphosphate Receptors Microscopy, Confocal Nuclear Envelope/metabolism,ultrastructure Photochemistry Protein Kinase C/metabolism Protein Transport/physiology Receptors, Cytoplasmic and Nuclear/agonists,metabolism Tumor Cells, Cultured
Chemicals
Calcium Channels ITPR1 protein, human Inositol 1,4,5-Trisphosphate Receptors Receptors, Cytoplasmic and Nuclear Inositol 1,4,5-Trisphosphate Protein Kinase C Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Echevarría Wihelma
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-801, USA.
Leite M Fatima
Guerra Mateus T
Zipfel Warren R
Nathanson Michael H
References (38)
38 references, click to expand
  1. High mobility of proteins in the mammalian cell nucleus.
    Nature. 2000 Apr 6;404(6778):604-9 PMID: 10766243
  2. Importin beta-mediated nuclear import of fibroblast growth factor receptor: role in cell proliferation.
    J Cell Biol. 2001 Mar 19;152(6):1307-12 PMID: 11257130
  3. The versatility and universality of calcium signalling.
    Nat Rev Mol Cell Biol. 2000 Oct;1(1):11-21 PMID: 11413485
  4. Nuclear localization of EGF receptor and its potential new role as a transcription factor.
    Nat Cell Biol. 2001 Sep;3(9):802-8 PMID: 11533659
  5. Multiphoton microscopy in biological research.
    Curr Opin Chem Biol. 2001 Oct;5(5):603-8 PMID: 11578936
  6. Ca2+ waves require sequential activation of inositol trisphosphate receptors and ryanodine receptors in pancreatic acini.
    Gastroenterology. 2002 Feb;122(2):415-27 PMID: 11832456
  7. Parallel single-cell monitoring of receptor-triggered membrane translocation of a calcium-sensing protein module.
    Science. 2002 Mar 8;295(5561):1910-2 PMID: 11884760
  8. Molecular basis for pacemaker cells in epithelia.
    J Biol Chem. 2002 May 3;277(18):16313-23 PMID: 11850419
  9. Atorvastatin treatment prevents alterations in coronary smooth muscle nuclear Ca2+ signaling in diabetic dyslipidemia.
    J Vasc Res. 2002 May-Jun;39(3):208-20 PMID: 12097819
  10. Epidermal growth factor-mediated activation of the ETS domain transcription factor Elk-1 requires nuclear calcium.
    J Biol Chem. 2002 Jul 26;277(30):27517-27 PMID: 11971908
  11. Fura-2 measurement of cytosolic free Ca2+ in monolayers and suspensions of various types of animal cells.
    J Cell Biol. 1987 Nov;105(5):2145-55 PMID: 3680375
  12. Molecular model for receptor-stimulated calcium spiking.
    Proc Natl Acad Sci U S A. 1988 Jul;85(14):5051-5 PMID: 2455890
  13. Two-photon laser scanning fluorescence microscopy.
    Science. 1990 Apr 6;248(4951):73-6 PMID: 2321027
  14. Stereospecific inositol 1,4,5-[32P]trisphosphate binding to isolated rat liver nuclei: evidence for inositol trisphosphate receptor-mediated calcium release from the nucleus.
    Proc Natl Acad Sci U S A. 1990 Dec;87(23):9270-4 PMID: 2174556
  15. Range of messenger action of calcium ion and inositol 1,4,5-trisphosphate.
    Science. 1992 Dec 11;258(5089):1812-5 PMID: 1465619
  16. Phosphoinositide signalling enzymes in rat liver nuclei: phosphoinositidase C isoform beta 1 is specifically, but not predominantly, located in the nucleus.
    Biochem J. 1993 Feb 1;289 ( Pt 3):617-20 PMID: 8382043
  17. Source of nuclear calcium signals.
    Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12458-62 PMID: 7809059
  18. ATP-dependent accumulation and inositol trisphosphate- or cyclic ADP-ribose-mediated release of Ca2+ from the nuclear envelope.
    Cell. 1995 Feb 10;80(3):439-44 PMID: 7859285
  19. Integrins and signal transduction pathways: the road taken.
    Science. 1995 Apr 14;268(5208):233-9 PMID: 7716514
  20. Type I, II, and III inositol 1,4,5-trisphosphate receptors are unequally susceptible to down-regulation and are expressed in markedly different proportions in different cell types.
    J Biol Chem. 1995 May 12;270(19):11678-83 PMID: 7744807
  21. Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis oocytes.
    Nature. 1995 Oct 5;377(6548):438-41 PMID: 7566122
  22. Diffusion across the nuclear envelope inhibited by depletion of the nuclear Ca2+ store.
    Science. 1995 Dec 15;270(5243):1835-8 PMID: 8525380
  23. Conformational states of the nuclear pore complex induced by depletion of nuclear Ca2+ stores.
    Science. 1996 Sep 27;273(5283):1875-7 PMID: 8791595
  24. Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy.
    Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10763-8 PMID: 8855254
  25. Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression.
    Nature. 1997 Jan 16;385(6613):260-5 PMID: 9000075
  26. Interphase nuclei of many mammalian cell types contain deep, dynamic, tubular membrane-bound invaginations of the nuclear envelope.
    J Cell Biol. 1997 Feb 10;136(3):531-44 PMID: 9024685
  27. Mechanism of long-range Ca2+ signalling in the nucleus of isolated rat hepatocytes.
    Biochem J. 1997 Sep 1;326 ( Pt 2):491-5 PMID: 9291123
  28. Nuclear calcium signalling by individual cytoplasmic calcium puffs.
    EMBO J. 1997 Dec 1;16(23):7166-73 PMID: 9384593
  29. Green fluorescent protein (GFP)-tagged cysteine-rich domains from protein kinase C as fluorescent indicators for diacylglycerol signaling in living cells.
    J Cell Biol. 1998 Feb 9;140(3):485-98 PMID: 9456311
  30. Translocation of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons.
    Nature. 1998 Mar 12;392(6672):198-202 PMID: 9515967
  31. Submillimolar levels of calcium regulates DNA structure at the dinucleotide repeat (TG/AC)n.
    Proc Natl Acad Sci U S A. 1998 May 26;95(11):5981-6 PMID: 9600903
  32. The nucleus of HeLa cell contains tubular structures for Ca2+ signalling.
    Biochem Biophys Res Commun. 1998 Jun 9;247(1):88-93 PMID: 9636660
  33. Isoform-specific function of single inositol 1,4,5-trisphosphate receptor channels.
    Biophys J. 1998 Aug;75(2):834-9 PMID: 9675184
  34. CBP: a signal-regulated transcriptional coactivator controlled by nuclear calcium and CaM kinase IV.
    Science. 1998 Sep 4;281(5382):1505-9 PMID: 9727976
  35. The Golgi apparatus is an inositol 1,4,5-trisphosphate-sensitive Ca2+ store, with functional properties distinct from those of the endoplasmic reticulum.
    EMBO J. 1998 Sep 15;17(18):5298-308 PMID: 9736609
  36. Protein kinase C as a molecular machine for decoding calcium and diacylglycerol signals.
    Cell. 1998 Oct 30;95(3):307-18 PMID: 9814702
  37. Type III InsP3 receptor channel stays open in the presence of increased calcium.
    Nature. 1998 Nov 5;396(6706):81-4 PMID: 9817204
  38. DREAM is a Ca2+-regulated transcriptional repressor.
    Nature. 1999 Mar 4;398(6722):80-4 PMID: 10078534
Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1465-7392
DOI
10.1038/ncb980
Published
2003-05-00
Pages
440-6
Language
English
Region
England
NLM ID
100890575
PMCID
PMC3572851
Subset
IM
Grants
NCRR NIH HHS · P41 RR004224-150063 · United States
NIDDK NIH HHS · R01 DK045710 · United States
NIDDK NIH HHS · R01 DK045710-06A2 · United States
NIDDK NIH HHS · R01 DK061747 · United States
Corrections
CommentIn
PMID: 15030997
External Links
PubMed source DOI: 10.1038/ncb980 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2