Home LiteratureArticle Details
PMID: 19395084 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Review

Regulation of Ca2+ entry by inositol lipids in mammalian cells by multiple mechanisms.

Cell calcium ·Vol. 45 ·No. 6 ·2009-06-00 ·Pages 527-34

Balla T

Abstract

Increased phosphoinositide turnover was first identified as an early signal transduction event initiated by cell surface receptors that were linked to calcium signaling. Subsequently, the generation of inositol 1,4,5-trisphosphate by phosphoinositide-specific phospholipase C enzymes was defined as the major link between inositide turnover and the cytosolic Ca(2+) rise in response to external stimulation. However, in the last decades, phosphoinositides have been emerging as major regulatory lipids involved in virtually every membrane-associated signaling process. Phosphoinositides regulate both the activity and the trafficking of almost all ion channels and transporters contributing to the maintenance of the ionic gradients that are essential for the proper functioning of all eukaryotic cells. Here we summarize the various means by which phosphoinositides affect ion channel functions with special emphasis on Ca(2+) signaling and outline the principles that govern the highly compartmentalized roles of these regulatory lipids.

MeSH Terms
Animals Calcium/metabolism Calcium Signaling/physiology Cell Membrane/physiology Humans Inositol 1,4,5-Trisphosphate/metabolism Ion Channels/metabolism Phosphatidylinositols/metabolism Phosphoinositide Phospholipase C/metabolism Signal Transduction
Chemicals
Ion Channels Phosphatidylinositols Inositol 1,4,5-Trisphosphate Phosphoinositide Phospholipase C Calcium
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Balla Tamas
Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, United States. ballat@mail.nih.gov
References (109)
109 references, click to expand
  1. trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry.
    Cell. 1996 May 31;85(5):661-71 PMID: 8646775
  2. Activity of the neuronal cold sensor TRPM8 is regulated by phospholipase C via the phospholipid phosphoinositol 4,5-bisphosphate.
    J Biol Chem. 2009 Jan 16;284(3):1570-82 PMID: 19019830
  3. A wortmannin-sensitive phosphatidylinositol 4-kinase that regulates hormone-sensitive pools of inositolphospholipids.
    Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5317-21 PMID: 7777504
  4. Acidic phospholipids, unsaturated fatty acids, and limited proteolysis mimic the effect of calmodulin on the purified erythrocyte Ca2+ - ATPase.
    J Biol Chem. 1981 Aug 25;256(16):8588-92 PMID: 6455424
  5. Sydney Ringer; physiological saline, calcium and the contraction of the heart.
    J Physiol. 2004 Mar 16;555(Pt 3):585-7 PMID: 14742734
  6. Mapping the interacting domains of STIM1 and Orai1 in Ca2+ release-activated Ca2+ channel activation.
    J Biol Chem. 2007 Oct 5;282(40):29448-56 PMID: 17702753
  7. Store-operated calcium channels.
    Physiol Rev. 2005 Apr;85(2):757-810 PMID: 15788710
  8. Essential and unique roles of PIP5K-gamma and -alpha in Fcgamma receptor-mediated phagocytosis.
    J Cell Biol. 2009 Jan 26;184(2):281-96 PMID: 19153220
  9. Regulation of ion transport proteins by membrane phosphoinositides.
    Nat Rev Neurosci. 2007 Dec;8(12):921-34 PMID: 17971783
  10. Light-regulated subcellular translocation of Drosophila TRPL channels induces long-term adaptation and modifies the light-induced current.
    Neuron. 2002 Mar 28;34(1):83-93 PMID: 11931743
  11. The Sec14-superfamily and the regulatory interface between phospholipid metabolism and membrane trafficking.
    Biochim Biophys Acta. 2007 Jun;1771(6):727-36 PMID: 17512778
  12. Integration of phosphoinositide- and calmodulin-mediated regulation of TRPC6.
    Mol Cell. 2007 Feb 23;25(4):491-503 PMID: 17317623
  13. Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate.
    Nature. 1983 Nov 3-9;306(5938):67-9 PMID: 6605482
  14. Localization and turnover of phosphatidylinositol 4,5-bisphosphate in caveolin-enriched membrane domains.
    J Biol Chem. 1996 Oct 25;271(43):26453-6 PMID: 8900109
  15. Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate.
    Curr Opin Neurobiol. 2005 Jun;15(3):370-8 PMID: 15922587
  16. Membranes are not just rafts.
    Chem Phys Lipids. 2006 Oct;144(1):1-3 PMID: 16945359
  17. A saturable receptor for 32P-inositol-1,4,5-triphosphate in hepatocytes and neutrophils.
    Nature. 1986 Feb 6-12;319(6053):514-6 PMID: 3003582
  18. Inositol phospholipids and cell surface receptor function.
    Biochim Biophys Acta. 1975 Mar 25;415(1):81-47 PMID: 164246
  19. Reversible binding and rapid diffusion of proteins in complex with inositol lipids serves to coordinate free movement with spatial information.
    J Cell Biol. 2009 Jan 26;184(2):297-308 PMID: 19153221
  20. Regulation of the epithelial sodium channel by membrane trafficking.
    Am J Physiol Renal Physiol. 2009 Jan;296(1):F10-24 PMID: 18508877
  21. PIP2 and PIP as determinants for ATP inhibition of KATP channels.
    Science. 1998 Nov 6;282(5391):1141-4 PMID: 9804555
  22. Role of STIM and Orai proteins in the store-operated calcium signaling pathway.
    Cell Calcium. 2007 Aug;42(2):173-82 PMID: 17602740
  23. Rapid chemically induced changes of PtdIns(4,5)P2 gate KCNQ ion channels.
    Science. 2006 Dec 1;314(5804):1454-7 PMID: 16990515
  24. Phospholipase C-gamma is required for agonist-induced Ca2+ entry.
    Cell. 2002 Nov 15;111(4):529-41 PMID: 12437926
  25. NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels.
    EMBO J. 2005 Dec 21;24(24):4211-23 PMID: 16319926
  26. Maintenance of hormone-sensitive phosphoinositide pools in the plasma membrane requires phosphatidylinositol 4-kinase IIIalpha.
    Mol Biol Cell. 2008 Feb;19(2):711-21 PMID: 18077555
  27. Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting.
    Science. 1993 Apr 2;260(5104):88-91 PMID: 8385367
  28. Emptying of intracellular Ca2+ stores releases a novel small messenger that stimulates Ca2+ influx.
    Nature. 1993 Aug 26;364(6440):809-14 PMID: 8355806
  29. PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels.
    J Physiol. 2005 Apr 1;564(Pt 1):117-29 PMID: 15677683
  30. Phospholipase Cgamma1 controls surface expression of TRPC3 through an intermolecular PH domain.
    Nature. 2005 Mar 3;434(7029):99-104 PMID: 15744307
  31. Phospholipid composition modulates the Na+-Ca2+ exchange activity of cardiac sarcolemma in reconstituted vesicles.
    Biochim Biophys Acta. 1988 Jan 22;937(2):258-68 PMID: 3276350
  32. Myosin light-chain kinase regulates endothelial calcium entry and endothelium-dependent vasodilation.
    FASEB J. 2001 Feb;15(2):282-4 PMID: 11156937
  33. Modulation of cardiac PIP2 by cardioactive hormones and other physiologically relevant interventions.
    Am J Physiol Cell Physiol. 2002 Jul;283(1):C223-34 PMID: 12055091
  34. Ca2+ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane.
    J Cell Biol. 2006 Sep 11;174(6):803-13 PMID: 16966422
  35. Phosphatidylinositol 4-kinase IIIbeta regulates the transport of ceramide between the endoplasmic reticulum and Golgi.
    J Biol Chem. 2006 Nov 24;281(47):36369-77 PMID: 17003043
  36. Phosphatidylinositol-4,5-bisphosphate regulates NMDA receptor activity through alpha-actinin.
    J Neurosci. 2007 May 16;27(20):5523-32 PMID: 17507574
  37. Phospholipase C in living cells: activation, inhibition, Ca2+ requirement, and regulation of M current.
    J Gen Physiol. 2005 Sep;126(3):243-62 PMID: 16129772
  38. Rapid vesicular translocation and insertion of TRP channels.
    Nat Cell Biol. 2004 Aug;6(8):709-20 PMID: 15258588
  39. PI(3,4,5)P3 and PI(4,5)P2 lipids target proteins with polybasic clusters to the plasma membrane.
    Science. 2006 Dec 1;314(5804):1458-61 PMID: 17095657
  40. Subcellular translocation of the eGFP-tagged TRPL channel in Drosophila photoreceptors requires activation of the phototransduction cascade.
    J Cell Sci. 2006 Jun 15;119(Pt 12):2592-603 PMID: 16735439
  41. Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones.
    Biochem J. 1983 Jun 15;212(3):733-47 PMID: 6309153
  42. Caveolin-1 contributes to assembly of store-operated Ca2+ influx channels by regulating plasma membrane localization of TRPC1.
    J Biol Chem. 2003 Jul 18;278(29):27208-15 PMID: 12732636
  43. Lipid rafts determine clustering of STIM1 in endoplasmic reticulum-plasma membrane junctions and regulation of store-operated Ca2+ entry (SOCE).
    J Biol Chem. 2008 Jun 20;283(25):17333-40 PMID: 18430726
  44. Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
    Nature. 1998 Feb 19;391(6669):803-6 PMID: 9486652
  45. Depletion of intracellular calcium stores activates a calcium current in mast cells.
    Nature. 1992 Jan 23;355(6358):353-6 PMID: 1309940
  46. Cloning of a human type II phosphatidylinositol 4-kinase reveals a novel lipid kinase family.
    J Biol Chem. 2001 May 18;276(20):16635-40 PMID: 11279162
  47. (Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms.
    Physiol Rev. 2006 Oct;86(4):1151-78 PMID: 17015487
  48. Visualization and manipulation of plasma membrane-endoplasmic reticulum contact sites indicates the presence of additional molecular components within the STIM1-Orai1 Complex.
    J Biol Chem. 2007 Oct 5;282(40):29678-90 PMID: 17684017
  49. New insights into the molecular mechanisms of store-operated Ca2+ signaling in T cells.
    Trends Mol Med. 2007 Mar;13(3):103-7 PMID: 17267286
  50. Intracellular trafficking of TRP channels.
    Cell Calcium. 2007 Aug;42(2):225-32 PMID: 17368756
  51. Dual regulation of voltage-gated calcium channels by PtdIns(4,5)P2.
    Nature. 2002 Oct 31;419(6910):947-52 PMID: 12410316
  52. The complex and intriguing lives of PIP2 with ion channels and transporters.
    Sci STKE. 2001 Dec 04;2001(111):re19 PMID: 11734659
  53. Phosphatidylinositol 4-kinases: old enzymes with emerging functions.
    Trends Cell Biol. 2006 Jul;16(7):351-61 PMID: 16793271
  54. Phosphoinositides regulate P2X4 ATP-gated channels through direct interactions.
    J Neurosci. 2008 Nov 26;28(48):12938-45 PMID: 19036987
  55. The lipid connection-regulation of voltage-gated Ca(2+) channels by phosphoinositides.
    Pflugers Arch. 2007 Oct;455(1):147-55 PMID: 17541627
  56. Regulation of plasma membrane Ca2+-ATPase by small GTPases and phosphoinositides in human platelets.
    J Biol Chem. 2000 Jun 30;275(26):19529-35 PMID: 10748016
  57. Dual control of cardiac Na+ Ca2+ exchange by PIP(2): electrophysiological analysis of direct and indirect mechanisms.
    J Physiol. 2007 Aug 1;582(Pt 3):991-1010 PMID: 17540705
  58. Rapid translocation and insertion of the epithelial Na+ channel in response to RhoA signaling.
    J Biol Chem. 2006 Sep 8;281(36):26520-7 PMID: 16829523
  59. Inositol trisphosphate, a novel second messenger in cellular signal transduction.
    Nature. 1984 Nov 22-28;312(5992):315-21 PMID: 6095092
  60. IGF-1 modulates N and L calcium channels in a PI 3-kinase-dependent manner.
    Neuron. 1997 Aug;19(2):421-9 PMID: 9292730
  61. Phosphatidylinositol 4-kinase is required for endosomal trafficking and degradation of the EGF receptor.
    J Cell Sci. 2006 Feb 1;119(Pt 3):571-81 PMID: 16443754
  62. Conformational coupling: a physiological calcium entry mechanism.
    Sci STKE. 2004 Jul 20;2004(243):pe33 PMID: 15280575
  63. On the physiological roles of PIP(2) at cardiac Na+ Ca2+ exchangers and K(ATP) channels: a long journey from membrane biophysics into cell biology.
    J Physiol. 2007 Aug 1;582(Pt 3):903-9 PMID: 17463041
  64. Membrane depolarization selectively inhibits receptor-operated calcium channels in human T (Jurkat) lymphoblasts.
    Biochim Biophys Acta. 1990 Aug 24;1027(2):130-40 PMID: 2168754
  65. Role of the phospholipase C-inositol 1,4,5-trisphosphate pathway in calcium release-activated calcium current and capacitative calcium entry.
    J Biol Chem. 2001 May 11;276(19):15945-52 PMID: 11278938
  66. TRP-PLIK, a bifunctional protein with kinase and ion channel activities.
    Science. 2001 Feb 9;291(5506):1043-7 PMID: 11161216
  67. Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi.
    Cell. 2003 Aug 8;114(3):299-310 PMID: 12914695
  68. PIP2 is a necessary cofactor for ion channel function: how and why?
    Annu Rev Biophys. 2008;37:175-95 PMID: 18573078
  69. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.
    Nature. 2001 Jun 21;411(6840):957-62 PMID: 11418861
  70. Rapidly inducible changes in phosphatidylinositol 4,5-bisphosphate levels influence multiple regulatory functions of the lipid in intact living cells.
    J Cell Biol. 2006 Nov 6;175(3):377-82 PMID: 17088424
  71. Dual regulation of TRPV1 by phosphoinositides.
    J Neurosci. 2007 Jun 27;27(26):7070-80 PMID: 17596456
  72. Regulation of KCNQ channels by manipulation of phosphoinositides.
    J Physiol. 2007 Aug 1;582(Pt 3):911-6 PMID: 17412763
  73. A requirement for lipid rafts in B cell receptor induced Ca(2+) flux.
    Curr Biol. 2000 Apr 6;10(7):393-6 PMID: 10753749
  74. Activation of TRPM7 channels by phospholipase C-coupled receptor agonists.
    J Biol Chem. 2007 Jan 5;282(1):232-9 PMID: 17095511
  75. STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels.
    Nat Cell Biol. 2006 Sep;8(9):1003-10 PMID: 16906149
  76. Activation of sarcoplasmic reticular Ca2+ transport ATPase by phosphorylation of an associated phosphatidylinositol.
    EMBO J. 1983;2(9):1543-8 PMID: 11892809
  77. Recent breakthroughs in the molecular mechanism of capacitative calcium entry (with thoughts on how we got here).
    Cell Calcium. 2007 Aug;42(2):103-10 PMID: 17349691
  78. Inhibition of agonist-stimulated inositol 1,4,5-trisphosphate production and calcium signaling by the myosin light chain kinase inhibitor, wortmannin.
    J Biol Chem. 1994 Mar 4;269(9):6528-35 PMID: 8120005
  79. Transient receptor potential channels meet phosphoinositides.
    EMBO J. 2008 Nov 5;27(21):2809-16 PMID: 18923420
  80. Phosphoinositides in cell regulation and membrane dynamics.
    Nature. 2006 Oct 12;443(7112):651-7 PMID: 17035995
  81. Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor.
    Nature. 2005 Jun 30;435(7046):1239-43 PMID: 15902207
  82. PI3K promotes voltage-dependent calcium channel trafficking to the plasma membrane.
    Nat Neurosci. 2004 Sep;7(9):939-46 PMID: 15311280
  83. Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores.
    Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6295-9 PMID: 8392195
  84. Requirements for distinct steps of phospholipase Cgamma2 regulation, membrane-raft-dependent targeting and subsequent enzyme activation in B-cell signalling.
    Biochem J. 2003 Aug 15;374(Pt 1):269-80 PMID: 12780340
  85. SOAR and the polybasic STIM1 domains gate and regulate Orai channels.
    Nat Cell Biol. 2009 Mar;11(3):337-43 PMID: 19182790
  86. Proteomic and functional evidence for a P2X7 receptor signalling complex.
    EMBO J. 2001 Nov 15;20(22):6347-58 PMID: 11707406
  87. The molecular choreography of a store-operated calcium channel.
    Nature. 2007 Mar 15;446(7133):284-7 PMID: 17361175
  88. PIP2 signaling in lipid domains: a critical re-evaluation.
    EMBO J. 2005 May 4;24(9):1664-73 PMID: 15861130
  89. Lipid and mechano-gated 2P domain K(+) channels.
    Curr Opin Cell Biol. 2001 Aug;13(4):422-8 PMID: 11454447
  90. Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400.
    Nature. 1989 Nov 2;342(6245):32-8 PMID: 2554142
  91. EEA1 links PI(3)K function to Rab5 regulation of endosome fusion.
    Nature. 1998 Jul 30;394(6692):494-8 PMID: 9697774
  92. Biochemical and biological functions of class I phosphatidylinositol transfer proteins.
    Biochim Biophys Acta. 2007 Jun;1771(6):677-91 PMID: 17490911
  93. Characterization of type II phosphatidylinositol 4-kinase isoforms reveals association of the enzymes with endosomal vesicular compartments.
    J Biol Chem. 2002 May 31;277(22):20041-50 PMID: 11923287
  94. Regulation of transient receptor potential (TRP) channels by phosphoinositides.
    Pflugers Arch. 2007 Oct;455(1):157-68 PMID: 17479281
  95. Native Store-operated Ca2+ Influx Requires the Channel Function of Orai1 and TRPC1.
    J Biol Chem. 2009 Apr 10;284(15):9733-41 PMID: 19228695
  96. STIM1 gates TRPC channels, but not Orai1, by electrostatic interaction.
    Mol Cell. 2008 Nov 7;32(3):439-48 PMID: 18995841
  97. Translocation of a calcium-permeable cation channel induced by insulin-like growth factor-I.
    Nat Cell Biol. 1999 Jul;1(3):165-70 PMID: 10559903
  98. A model for receptor-regulated calcium entry.
    Cell Calcium. 1986 Feb;7(1):1-12 PMID: 2420465
  99. Phosphoinositides are required for store-mediated calcium entry in human platelets.
    J Biol Chem. 2000 Mar 31;275(13):9110-3 PMID: 10734043
  100. Calcium signals mediated by STIM and Orai proteins--a new paradigm in inter-organelle communication.
    Biochim Biophys Acta. 2006 Nov;1763(11):1161-8 PMID: 17084918
  101. Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol.
    Biochem J. 1983 Jun 15;212(3):849-58 PMID: 6309155
  102. K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
    Nature. 1996 Nov 7;384(6604):78-80 PMID: 8900282
  103. PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain.
    Nat Neurosci. 2005 May;8(5):626-34 PMID: 15852009
  104. Functional recovery from desensitization of vanilloid receptor TRPV1 requires resynthesis of phosphatidylinositol 4,5-bisphosphate.
    J Neurosci. 2005 May 11;25(19):4835-43 PMID: 15888659
  105. Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2.
    Science. 1996 Aug 16;273(5277):956-9 PMID: 8688080
  106. The comeback of mitochondria to calcium signalling.
    Cell Calcium. 2000 Nov-Dec;28(5-6):279-83 PMID: 11115367
  107. Live-cell imaging reveals sequential oligomerization and local plasma membrane targeting of stromal interaction molecule 1 after Ca2+ store depletion.
    Proc Natl Acad Sci U S A. 2007 May 29;104(22):9301-6 PMID: 17517596
  108. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction.
    Neuron. 1989 Apr;2(4):1313-23 PMID: 2516726
  109. Differential regulation of muscarinic acetylcholine receptor-sensitive polyphosphoinositide pools and consequences for signaling in human neuroblastoma cells.
    J Biol Chem. 1998 Feb 27;273(9):5037-46 PMID: 9478953
Article Info
Journal
Cell calcium
Abbr.
Cell Calcium
ISSN
1532-1991
DOI
10.1016/j.ceca.2009.03.013
Email
ballat@mail.nih.gov
Published
2009-06-00
Epub
2009-00-22
Pages
527-34
Language
English
Region
Netherlands
NLM ID
8006226
PMCID
PMC2695834
Subset
IM
Grants
Intramural NIH HHS · Z01 HD000196-10 · United States
External Links
PubMed source DOI: 10.1016/j.ceca.2009.03.013 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