title: Phosphoinositide signaling: new tools and insights.
abstract: Phosphoinositides constitute only a small fraction of cellular phospholipids, yet their importance in the regulation of cellular functions can hardly be overstated. The rapid metabolic response of phosphoinositides after stimulation of certain cell surface receptors was the first indication that these lipids could serve as regulatory molecules. These early observations opened research areas that ultimately clarified the plasma membrane role of phosphoinositides in Ca(2+) signaling. However, research of the last 10 years has revealed a much broader range of processes dependent on phosphoinositides. These lipids control organelle biology by regulating vesicular trafficking, and they modulate lipid distribution and metabolism more generally via their close relationship with lipid transfer proteins. Phosphoinositides also regulate ion channels, pumps, and transporters as well as both endocytic and exocytic processes. The significance of phosphoinositides found within the nucleus is still poorly understood, and a whole new research concerns the highly phosphorylated inositols that also appear to control multiple nuclear processes. The expansion of research and interest in phosphoinositides naturally created a demand for new approaches to determine where, within the cell, these lipids exert their effects. Imaging of phosphoinositide dynamics within live cells has become a standard cell biological method. These new tools not only helped us localize phosphoinositides within the cell but also taught us how tightly phosphoinositide control can be linked with distinct effector protein complexes. The recent progress allows us to understand the underlying causes of certain human diseases and design new strategies for therapeutic interventions.
authors.affiliation: 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, Maryland, USA. ballat@mail.nih.gov
authors.forename: Tamas
authors.initials: T
authors.lastname: Balla
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Szentpetery
authors.forename: Yeun Ju
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D010716:Phosphatidylinositols / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D010716:Phosphatidylinositols
references.citation: J Biol Chem. 1981 Aug 25;256(16):8588-92
references.pmid: 6455424
references.citation: Physiol Rev. 2000 Oct;80(4):1291-335
references.pmid: 11015615
references.citation: Neuron. 2001 Oct 11;32(1):79-88
references.pmid: 11604140
references.citation: Mol Biol Cell. 2008 Apr;19(4):1415-26
references.pmid: 18256276
references.citation: J Physiol. 2007 Sep 15;583(Pt 3):875-89
references.pmid: 17615106
references.citation: Immunity. 2002 Mar;16(3):441-51
references.pmid: 11911828
references.citation: Biochim Biophys Acta. 2006 May-Jun;1761(5-6):505-8
references.pmid: 16574480
references.citation: Nat Rev Neurosci. 2007 Dec;8(12):921-34
references.pmid: 17971783
references.citation: Biochem J. 2000 Oct 1;351(Pt 1):19-31
references.pmid: 11001876
references.citation: Cytometry A. 2006 Dec 1;69(12):1174-83
references.pmid: 17131383
references.citation: Prog Lipid Res. 2005 Jul;44(4):185-206
references.pmid: 15896848
references.citation: J Biol Chem. 1997 May 16;272(20):13236-41
references.pmid: 9148941
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18556-61
references.pmid: 17116893
references.citation: Cell Calcium. 2009 Jun;45(6):554-65
references.pmid: 19376575
references.citation: J Biol Chem. 2008 Feb 15;283(7):4344-51
references.pmid: 18073207
references.citation: J Cell Biol. 2002 Apr 1;157(1):63-77
references.pmid: 11916983
references.citation: J Biol Chem. 1953 Aug;203(2):967-77
references.pmid: 13084667
references.citation: Nature. 2008 Feb 21;451(7181):1013-7
references.pmid: 18288197
references.citation: IUBMB Life. 2006 Aug;58(8):451-6
references.pmid: 16916781
references.citation: Vitam Horm. 2007;76:45-65
references.pmid: 17628171
references.citation: Nat Rev Mol Cell Biol. 2008 Feb;9(2):99-111
references.pmid: 18216767
references.citation: Biochem J. 2008 Nov 1;415(3):455-66
references.pmid: 18601652
references.citation: Mol Cell Biochem. 2006 Jun;286(1-2):23-31
references.pmid: 16601923
references.citation: Cell. 2009 Mar 20;136(6):1110-21
references.pmid: 19303853
references.citation: Annu Rev Physiol. 2003;65:761-89
references.pmid: 12471164
references.citation: Mol Cell. 2007 Feb 23;25(4):491-503
references.pmid: 17317623
references.citation: Nature. 1983 Nov 3-9;306(5938):67-9
references.pmid: 6605482
references.citation: Biochem J. 2002 May 1;363(Pt 3):657-66
references.pmid: 11964166
references.citation: EMBO J. 1991 Nov;10(11):3207-14
references.pmid: 1655412
references.citation: Nature. 1982 Apr 8;296(5857):492-3
references.pmid: 7070496
references.citation: J Neurosci. 2004 Dec 1;24(48):10980-92
references.pmid: 15574748
references.citation: Biochem J. 1993 Feb 1;289 ( Pt 3):617-20
references.pmid: 8382043
references.citation: Biochim Biophys Acta. 1975 Mar 25;415(1):81-47
references.pmid: 164246
references.citation: J Neurosci. 2005 Mar 9;25(10):2557-65
references.pmid: 15758165
references.citation: Dev Cell. 2002 May;2(5):593-605
references.pmid: 12015967
references.citation: Science. 1998 Nov 6;282(5391):1141-4
references.pmid: 9804555
references.citation: J Cell Biol. 1998 Oct 19;143(2):501-10
references.pmid: 9786958
references.citation: Mol Biol Cell. 2006 Jun;17(6):2498-512
references.pmid: 16540520
references.citation: Nature. 1995 Mar 9;374(6518):173-7
references.pmid: 7877690
references.citation: Mol Cell. 1999 Jun;3(6):805-11
references.pmid: 10394369
references.citation: Science. 2006 Dec 1;314(5804):1454-7
references.pmid: 16990515
references.citation: Mol Biol Cell. 2008 Feb;19(2):711-21
references.pmid: 18077555
references.citation: Science. 1993 Apr 2;260(5104):88-91
references.pmid: 8385367
references.citation: Nat Cell Biol. 2005 Mar;7(3):225-34
references.pmid: 15723057
references.citation: Nature. 2005 Sep 1;437(7055):154-8
references.pmid: 16136145
references.citation: Mol Cell. 2004 Mar 12;13(5):677-88
references.pmid: 15023338
references.citation: Cell Signal. 1993 Sep;5(5):565-81
references.pmid: 8312134
references.citation: Biochim Biophys Acta. 1967 Dec 5;144(3):649-58
references.pmid: 4294903
references.citation: Cell Host Microbe. 2009 Mar 19;5(3):298-307
references.pmid: 19286138
references.citation: Biochem Soc Trans. 2004 Nov;32(Pt 5):707-11
references.pmid: 15493994
references.citation: Cell. 2003 Jul 11;114(1):99-111
references.pmid: 12859901
references.citation: J Cell Biol. 2007 Dec 17;179(6):1247-59
references.pmid: 18086920
references.citation: Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1406-10
references.pmid: 7877991
references.citation: Trends Cell Biol. 2005 Oct;15(10):540-7
references.pmid: 16139503
references.citation: Biochem J. 1983 Jun 15;212(3):733-47
references.pmid: 6309153
references.citation: J Biol Chem. 2006 Nov 24;281(47):36369-77
references.pmid: 17003043
references.citation: J Cell Sci. 2001 Jul;114(Pt 13):2501-11
references.pmid: 11559758
references.citation: Mol Cell. 2008 Feb 1;29(2):191-206
references.pmid: 18243114
references.citation: J Gen Physiol. 2005 Sep;126(3):243-62
references.pmid: 16129772
references.citation: J Cell Biol. 2007 Jun 18;177(6):1091-104
references.pmid: 17576801
references.citation: Nature. 1998 Feb 19;391(6669):803-6
references.pmid: 9486652
references.citation: J Biol Chem. 1997 Jan 24;272(4):2477-85
references.pmid: 8999962
references.citation: J Cell Biol. 2008 Jul 28;182(2):355-66
references.pmid: 18644890
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8454-9
references.pmid: 15939867
references.citation: J Cell Biol. 2005 Aug 15;170(4):521-6
references.pmid: 16103222
references.citation: Science. 2002 Jan 11;295(5553):325-8
references.pmid: 11729268
references.citation: Trends Biochem Sci. 2005 Apr;30(4):194-204
references.pmid: 15817396
references.citation: Genetics. 2004 Jul;167(3):1213-23
references.pmid: 15280236
references.citation: J Biol Chem. 2007 Oct 5;282(40):29678-90
references.pmid: 17684017
references.citation: Annu Rev Biophys Biomol Struct. 2007;36:451-77
references.pmid: 17477841
references.citation: Nature. 2007 Dec 13;450(7172):1106-10
references.pmid: 18033247
references.citation: J Biol Chem. 1989 Nov 5;264(31):18489-93
references.pmid: 2553710
references.citation: J Biol Chem. 2004 Oct 22;279(43):44683-9
references.pmid: 15271978
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8262-9
references.pmid: 15146067
references.citation: Sci STKE. 2001 Dec 04;2001(111):re19
references.pmid: 11734659
references.citation: Trends Cell Biol. 2006 Jul;16(7):351-61
references.pmid: 16793271
references.citation: J Cell Biol. 2002 Jul 22;158(2):209-14
references.pmid: 12119359
references.citation: Pflugers Arch. 2007 Oct;455(1):147-55
references.pmid: 17541627
references.citation: Cell. 1993 Sep 10;74(5):919-28
references.pmid: 8374957
references.citation: J Cell Sci. 2005 May 15;118(Pt 10):2093-104
references.pmid: 15890985
references.citation: J Cell Biol. 2008 Dec 15;183(6):1061-74
references.pmid: 19075114
references.citation: Nature. 1996 Jan 25;379(6563):353-7
references.pmid: 8552192
references.citation: J Biol Chem. 1996 May 17;271(20):12088-94
references.pmid: 8662589
references.citation: J Biol Chem. 1999 Nov 26;274(48):34294-300
references.pmid: 10567405
references.citation: Anal Biochem. 1988 May 1;170(2):308-15
references.pmid: 3394931
references.citation: J Physiol. 2007 Aug 1;582(Pt 3):991-1010
references.pmid: 17540705
references.citation: J Cell Biol. 2007 Jul 2;178(1):15-22
references.pmid: 17591919
references.citation: Curr Protoc Cell Biol. 2009 Mar;Chapter 24:Unit 24.4
references.pmid: 19283730
references.citation: J Biol Chem. 2005 Feb 18;280(7):6047-54
references.pmid: 15576365
references.citation: Mol Biol Cell. 2005 Mar;16(3):1282-95
references.pmid: 15635101
references.citation: Virology. 2009 Apr 25;387(1):5-10
references.pmid: 19304308
references.citation: Methods Enzymol. 2005;404:422-31
references.pmid: 16413288
references.citation: J Cell Sci. 2006 Feb 1;119(Pt 3):571-81
references.pmid: 16443754
references.citation: Annu Rev Biochem. 2001;70:281-312
references.pmid: 11395409
references.citation: Cell. 1992 Sep 4;70(5):765-75
references.pmid: 1516133
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11286-91
references.pmid: 11005844
references.citation: J Biol Chem. 2001 Oct 26;276(43):40183-9
references.pmid: 11526106
references.citation: Cell. 2003 Aug 8;114(3):299-310
references.pmid: 12914695
references.citation: J Cell Biol. 2005 Dec 19;171(6):967-79
references.pmid: 16365163
references.citation: Annu Rev Biophys. 2008;37:175-95
references.pmid: 18573078
references.citation: J Cell Sci. 2002 Apr 15;115(Pt 8):1769-75
references.pmid: 11950893
references.citation: J Cell Biol. 2006 Nov 6;175(3):377-82
references.pmid: 17088424
references.citation: Curr Biol. 1998 Jun 18;8(13):729-39
references.pmid: 9651677
references.citation: J Neurosci. 2007 Jun 27;27(26):7070-80
references.pmid: 17596456
references.citation: Mol Biol Cell. 2004 Aug;15(8):3567-79
references.pmid: 15169871
references.citation: Nature. 2001 Jun 21;411(6840):957-62
references.pmid: 11418861
references.citation: Mol Biol Cell. 2007 Jul;18(7):2646-55
references.pmid: 17494868
references.citation: Mol Biol Cell. 2001 Aug;12(8):2396-411
references.pmid: 11514624
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8448-53
references.pmid: 15939868
references.citation: J Biol Chem. 1998 May 22;273(21):13189-96
references.pmid: 9582361
references.citation: Annu Rev Physiol. 2003;65:791-815
references.pmid: 12518000
references.citation: Traffic. 2005 Dec;6(12):1157-72
references.pmid: 16262726
references.citation: Immunity. 2003 Nov;19(5):669-78
references.pmid: 14614854
references.citation: Science. 1999 Jul 2;285(5424):96-100
references.pmid: 10390371
references.citation: Biochem J. 1993 Dec 1;296 ( Pt 2):297-301
references.pmid: 8257416
references.citation: Nat Genet. 2000 Nov;26(3):379-82
references.pmid: 11062485
references.citation: J Biol Chem. 1992 Mar 15;267(8):5078-84
references.pmid: 1312084
references.citation: Nature. 2003 Dec 18;426(6968):803-9
references.pmid: 14685229
references.citation: EMBO J. 1983;2(9):1543-8
references.pmid: 11892809
references.citation: EMBO J. 2000 Sep 1;19(17):4577-88
references.pmid: 10970851
references.citation: Cell Calcium. 2007 Aug;42(2):103-10
references.pmid: 17349691
references.citation: J Cell Biol. 1999 Aug 23;146(4):755-64
references.pmid: 10459011
references.citation: Cell. 2008 May 2;133(3):475-85
references.pmid: 18455988
references.citation: EMBO J. 2008 Nov 5;27(21):2809-16
references.pmid: 18923420
references.citation: Nature. 2005 Jun 30;435(7046):1239-43
references.pmid: 15902207
references.citation: J Cell Sci. 2003 Aug 1;116(Pt 15):3037-40
references.pmid: 12829733
references.citation: Adv Enzyme Regul. 2007;47:10-25
references.pmid: 17467778
references.citation: Nature. 2004 Oct 21;431(7011):1007-11
references.pmid: 15496927
references.citation: Mol Biol Cell. 2006 Jun;17(6):2604-16
references.pmid: 16571669
references.citation: Biochim Biophys Acta. 2006 Aug;1761(8):957-67
references.pmid: 16702024
references.citation: Nature. 1996 Apr 18;380(6575):595-602
references.pmid: 8602259
references.citation: Science. 2000 Feb 11;287(5455):1037-40
references.pmid: 10669415
references.citation: J Cell Biol. 2004 Dec 20;167(6):1005-10
references.pmid: 15611330
references.citation: Biochim Biophys Acta. 2008 Jan;1784(1):159-85
references.pmid: 17997386
references.citation: Nature. 2007 Mar 15;446(7133):284-7
references.pmid: 17361175
references.citation: Mol Cell Biol. 1999 Jan;19(1):623-34
references.pmid: 9858586
references.citation: J Cell Biol. 2001 Sep 3;154(5):1007-17
references.pmid: 11535619
references.citation: Methods Enzymol. 2003;366:64-84
references.pmid: 14674240
references.citation: Mol Cell. 2005 Jan 21;17(2):181-91
references.pmid: 15664188
references.citation: J Membr Biol. 2003 Jul 15;194(2):77-89
references.pmid: 14502432
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15352-7
references.pmid: 17881569
references.citation: Cancer Cell. 2005 Jun;7(6):561-73
references.pmid: 15950905
references.citation: J Cell Biol. 1989 Apr;108(4):1271-81
references.pmid: 2466847
references.citation: Nature. 1998 Jul 30;394(6692):494-8
references.pmid: 9697774
references.citation: Biochim Biophys Acta. 2007 Jun;1771(6):677-91
references.pmid: 17490911
references.citation: Mol Cell Biol. 1998 Jul;18(7):4131-40
references.pmid: 9632797
references.citation: Proc Natl Acad Sci U S A. 2009 May 5;106(18):7577-82
references.pmid: 19376974
references.citation: Mol Biol Cell. 1998 Dec;9(12):3547-60
references.pmid: 9843587
references.citation: Proc Natl Acad Sci U S A. 1996 May 14;93(10):4604-7
references.pmid: 8643450
references.citation: J Cell Biol. 2007 Oct 8;179(1):101-15
references.pmid: 17923531
references.citation: J Biol Chem. 2009 Jan 16;284(3):1570-82
references.pmid: 19019830
references.citation: Cell Biol Int. 2008 Jun;32(6):591-604
references.pmid: 18304842
references.citation: Cell. 1993 Aug 13;74(3):405-7
references.pmid: 8394217
references.citation: Biochem Biophys Res Commun. 1992 Aug 31;187(1):158-63
references.pmid: 1325787
references.citation: Trends Cell Biol. 2005 May;15(5):259-68
references.pmid: 15866030
references.citation: J Cell Biol. 1998 Oct 5;143(1):65-79
references.pmid: 9763421
references.citation: J Biol Chem. 2002 May 31;277(22):20041-50
references.pmid: 11923287
references.citation: J Cell Biol. 2006 Apr 10;173(1):107-19
references.pmid: 16585271
references.citation: Curr Biol. 1998 Mar 12;8(6):343-6
references.pmid: 9512420
references.citation: J Biol Chem. 1960 Jun;235:PC23-4
references.pmid: 13828720
references.citation: J Cell Sci. 2008 May 1;121(Pt 9):1488-94
references.pmid: 18411250
references.citation: Cell. 1998 Oct 30;95(3):307-18
references.pmid: 9814702
references.citation: Cell Calcium. 1986 Feb;7(1):1-12
references.pmid: 2420465
references.citation: Science. 2003 Jan 3;299(5603):114-6
references.pmid: 12434012
references.citation: Biochem J. 1990 May 15;268(1):15-25
references.pmid: 2160809
references.citation: Nat Struct Mol Biol. 2006 Dec;13(12):1135-40
references.pmid: 17115053
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3793-8
references.pmid: 17360432
references.citation: Mol Cell. 2008 Aug 8;31(3):383-94
references.pmid: 18691970
references.citation: Biochem J. 1983 Jun 15;212(3):849-58
references.pmid: 6309155
references.citation: Nature. 2006 May 18;441(7091):366-70
references.pmid: 16625210
references.citation: Biochem J. 1990 Jan 15;265(2):421-7
references.pmid: 2154189
references.citation: Nature. 1993 Dec 9;366(6455):572-5
references.pmid: 8255295
references.citation: Nat Cell Biol. 2004 May;6(5):393-404
references.pmid: 15107860
references.citation: J Biol Chem. 1999 Apr 16;274(16):10983-9
references.pmid: 10196179
references.citation: Nat Cell Biol. 2005 Sep;7(9):880-6
references.pmid: 16100512
references.citation: Curr Biol. 2002 Apr 30;12(9):695-704
references.pmid: 12007412
references.citation: Nat Neurosci. 2005 May;8(5):626-34
references.pmid: 15852009
references.citation: Cell Mol Life Sci. 2003 Oct;60(10):2084-99
references.pmid: 14618257
references.citation: J Neurosci. 2005 May 11;25(19):4835-43
references.pmid: 15888659
references.citation: Science. 1996 Aug 16;273(5277):956-9
references.pmid: 8688080
references.citation: Mol Biol Cell. 2001 Jun;12(6):1633-44
references.pmid: 11408574
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5204-9
references.pmid: 15793002
references.citation: Nat Cell Biol. 1999 Aug;1(4):234-41
references.pmid: 10559922
references.citation: Biochim Biophys Acta. 2005 Jul 10;1744(3):396-405
references.pmid: 15979509
references.citation: J Biol Chem. 2009 Jan 23;284(4):2106-13
references.pmid: 19047057
references.citation: Mol Cell. 1998 Jul;2(1):157-62
references.pmid: 9702203
references.citation: Trends Cell Biol. 2008 May;18(5):220-7
references.pmid: 18396046
references.citation: Nature. 2007 Sep 6;449(7158):62-7
references.pmid: 17687330