title: Activation and regulation of store-operated calcium entry.
abstract: The process of store-operated Ca(2+) entry (SOCE), whereby Ca(2+) influx across the plasma membrane is activated in response to depletion of intracellular Ca(2+) stores in the endoplasmic reticulum (ER), has been under investigation for greater than 25 years; however, only in the past 5 years have we come to understand this mechanism at the molecular level. A surge of recent experimentation indicates that STIM molecules function as Ca(2+) sensors within the ER that, upon Ca(2+) store depletion, rearrange to sites very near to the plasma membrane. At these plasma membrane-ER junctions, STIM interacts with and activates SOCE channels of the Orai family. The molecular and biophysical data that have led to these findings are discussed in this review, as are several controversies within this rapidly expanding field.
authors.affiliation: Laboratory of Signal Transduction, National Institute of Environmental Health Sciences-NIH, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Smyth
authors.forename: Sung-Yong
authors.initials: SY
authors.lastname: Hwang
authors.forename: Takuro
authors.initials: T
authors.lastname: Tomita
authors.forename: Wayne I
authors.initials: WI
authors.lastname: DeHaven
authors.forename: Jason C
authors.initials: JC
authors.lastname: Mercer
authors.forename: James W
authors.initials: JW
authors.lastname: Putney
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D008565:Membrane Proteins; D000071740:ORAI1 Protein; C513279:STIM2 protein, human; C502662:Stim protein, Drosophila; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D050052:TRPC Cation Channels; C510747:olf186-F protein, Drosophila; D002118:Calcium
references.citation: FASEB J. 2009 Mar;23(3):894-905
references.pmid: 18978154
references.citation: J Biol Chem. 2006 Sep 1;281(35):25250-8
references.pmid: 16822861
references.citation: Mol Cell Biol. 2008 Sep;28(17):5209-22
references.pmid: 18591248
references.citation: Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3168-73
references.pmid: 11248050
references.citation: J Biol Chem. 2007 Oct 5;282(40):29448-56
references.pmid: 17702753
references.citation: J Physiol. 2004 Sep 15;559(Pt 3):739-50
references.pmid: 15254149
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13668-73
references.pmid: 18757751
references.citation: Cell. 2008 Oct 3;135(1):110-22
references.pmid: 18854159
references.citation: Physiol Rev. 2005 Apr;85(2):757-810
references.pmid: 15788710
references.citation: Nature. 1998 Apr 30;392(6679):933-6
references.pmid: 9582075
references.citation: J Physiol. 2005 Feb 1;562(Pt 3):697-706
references.pmid: 15513935
references.citation: Nature. 2006 Sep 14;443(7108):226-9
references.pmid: 16921385
references.citation: Am J Physiol. 1990 Jun;258(6 Pt 1):C1006-15
references.pmid: 2360617
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15495-500
references.pmid: 19706428
references.citation: Curr Biol. 2006 Jul 25;16(14):1465-70
references.pmid: 16860747
references.citation: Nat Immunol. 2008 Jan;9(1):89-96
references.pmid: 18059270
references.citation: Biochem Biophys Res Commun. 2007 Apr 27;356(1):45-52
references.pmid: 17343823
references.citation: J Physiol. 2008 Jul 1;586(13):3061-73
references.pmid: 18403424
references.citation: J Gen Physiol. 2006 Sep;128(3):373-86
references.pmid: 16940559
references.citation: J Biol Chem. 2009 Jan 9;284(2):728-32
references.pmid: 19019825
references.citation: J Biol Chem. 2009 Aug 7;284(32):21696-706
references.pmid: 19506081
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1392-6
references.pmid: 14734814
references.citation: J Biol Chem. 1995 Jun 16;270(24):14445-51
references.pmid: 7540169
references.citation: Nat Cell Biol. 2006 Jul;8(7):771-3
references.pmid: 16733527
references.citation: Cell Calcium. 2007 Aug;42(2):173-82
references.pmid: 17602740
references.citation: Cancer Res. 1997 Oct 15;57(20):4493-7
references.pmid: 9377559
references.citation: J Cell Sci. 2008 Mar 15;121(Pt 6):762-72
references.pmid: 18285445
references.citation: Cell Calcium. 2007 Mar;41(3):249-60
references.pmid: 17064762
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4040-5
references.pmid: 16537481
references.citation: J Biol Chem. 2000 Dec 8;275(49):38710-5
references.pmid: 10991950
references.citation: Cell Calcium. 2008 Dec;44(6):533-44
references.pmid: 18452988
references.citation: J Cell Biol. 1988 Dec;107(6 Pt 2):2533-9
references.pmid: 3204119
references.citation: Biochem Biophys Res Commun. 2008 Apr 25;369(1):240-6
references.pmid: 18166150
references.citation: J Physiol. 2008 Jul 1;586(13):3035-42
references.pmid: 18499724
references.citation: J Cell Biol. 2006 Sep 11;174(6):803-13
references.pmid: 16966422
references.citation: J Cell Sci. 2007 Nov 1;120(Pt 21):3762-71
references.pmid: 17925382
references.citation: Circ Res. 1972 Jan;30(1):44-54
references.pmid: 5007527
references.citation: Curr Biol. 2006 Oct 24;16(20):2073-9
references.pmid: 16978865
references.citation: J Biol Chem. 2006 Aug 25;281(34):24979-90
references.pmid: 16807233
references.citation: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7461-6
references.pmid: 12032305
references.citation: J Cell Biol. 2006 Sep 11;174(6):815-25
references.pmid: 16966423
references.citation: J Biol Chem. 2008 Jun 20;283(25):17333-40
references.pmid: 18430726
references.citation: Cell. 2007 Dec 28;131(7):1327-39
references.pmid: 18160041
references.citation: J Biol Chem. 2009 Jul 31;284(31):21027-35
references.pmid: 19483082
references.citation: Nature. 2008 Jul 24;454(7203):538-42
references.pmid: 18596693
references.citation: Nature. 1992 Jan 23;355(6358):353-6
references.pmid: 1309940
references.citation: Nature. 2006 May 11;441(7090):179-85
references.pmid: 16582901
references.citation: Science. 2006 May 26;312(5777):1220-3
references.pmid: 16645049
references.citation: J Biol Chem. 2007 Oct 5;282(40):29678-90
references.pmid: 17684017
references.citation: J Biol Chem. 2007 Jun 15;282(24):17548-56
references.pmid: 17452328
references.citation: Nature. 1998 Dec 3;396(6710):478-82
references.pmid: 9853757
references.citation: J Biol Chem. 2008 Nov 14;283(46):31348-55
references.pmid: 18806259
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16704-9
references.pmid: 17075073
references.citation: J Biol Chem. 2006 Jul 28;281(30):20661-20665
references.pmid: 16766533
references.citation: Biochem J. 1994 Feb 1;297 ( Pt 3):437-40
references.pmid: 8110177
references.citation: J Biol Chem. 2008 Jul 18;283(29):20261-7
references.pmid: 18499656
references.citation: J Biol Chem. 1999 Nov 26;274(48):33995-8
references.pmid: 10567364
references.citation: Pflugers Arch. 2006 Apr;452(1):43-52
references.pmid: 16283206
references.citation: Cell Regul. 1991 Nov;2(11):915-25
references.pmid: 1809398
references.citation: J Biol Chem. 2000 Dec 15;275(50):39055-60
references.pmid: 10984475
references.citation: J Biol Chem. 2009 Jul 17;284(29):19164-8
references.pmid: 19487696
references.citation: J Biol Chem. 2006 Nov 24;281(47):35855-62
references.pmid: 17020874
references.citation: Nat Rev Mol Cell Biol. 2000 Oct;1(1):11-21
references.pmid: 11413485
references.citation: J Physiol. 2008 Jul 1;586(13):3043-54
references.pmid: 18467365
references.citation: Nat Cell Biol. 2007 Jun;9(6):636-45
references.pmid: 17486119
references.citation: J Biol Chem. 1998 Apr 10;273(15):9297-305
references.pmid: 9535924
references.citation: Acta Physiol (Oxf). 2009 Jan;195(1):29-35
references.pmid: 18983453
references.citation: Mol Biol Cell. 2008 Jul;19(7):2802-17
references.pmid: 18448669
references.citation: J Physiol. 2008 Nov 15;586(22):5383-401
references.pmid: 18832420
references.citation: J Gen Physiol. 1995 Feb;105(2):209-26
references.pmid: 7760017
references.citation: J Biol Chem. 2007 Mar 23;282(12):9105-16
references.pmid: 17224452
references.citation: J Biol Chem. 2001 May 11;276(19):15945-52
references.pmid: 11278938
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Nov;279(5):L815-24
references.pmid: 11053015
references.citation: J Exp Med. 2002 Mar 18;195(6):673-81
references.pmid: 11901194
references.citation: J Physiol. 2009 May 15;587(Pt 10):2275-98
references.pmid: 19332491
references.citation: Channels (Austin). 2007 Jul-Aug;1(4):246-52
references.pmid: 18711860
references.citation: Cell Calcium. 1999 Mar;25(3):237-46
references.pmid: 10378085
references.citation: J Cell Biol. 2005 May 9;169(3):435-45
references.pmid: 15866891
references.citation: Arterioscler Thromb Vasc Biol. 2001 Apr;21(4):509-15
references.pmid: 11304465
references.citation: Cell Calcium. 2007 Aug;42(2):123-32
references.pmid: 17382385
references.citation: J Biol Chem. 2008 Jul 11;283(28):19265-73
references.pmid: 18487204
references.citation: Nat Immunol. 2008 Apr;9(4):432-43
references.pmid: 18327260
references.citation: Cell. 2009 Mar 6;136(5):876-90
references.pmid: 19249086
references.citation: Am J Physiol Cell Physiol. 2008 Nov;295(5):C1133-40
references.pmid: 18768920
references.citation: J Biol Chem. 2007 Jul 6;282(27):19375-84
references.pmid: 17463004
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17401-6
references.pmid: 19805124
references.citation: Curr Biol. 2005 Jul 12;15(13):1235-41
references.pmid: 16005298
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2895-900
references.pmid: 18287061
references.citation: Curr Biol. 2008 Feb 12;18(3):177-82
references.pmid: 18249114
references.citation: Nat Cell Biol. 2006 Sep;8(9):1003-10
references.pmid: 16906149
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9357-62
references.pmid: 16751269
references.citation: Biochim Biophys Acta. 2000 Aug 31;1481(1):147-55
references.pmid: 11004585
references.citation: J Physiol. 2006 Jan 15;570(Pt 2):219-35
references.pmid: 16284075
references.citation: Nat Cell Biol. 2009 Jun;11(6):669-77
references.pmid: 19488056
references.citation: J Physiol. 2008 Jul 1;586(13):3055-9
references.pmid: 18388136
references.citation: J Physiol. 1993 Jun;465:359-86
references.pmid: 8229840
references.citation: J Biol Chem. 2005 Sep 2;280(35):30788-96
references.pmid: 15987684
references.citation: Nat Cell Biol. 2009 Apr;11(4):433-42
references.pmid: 19287379
references.citation: Cell Calcium. 2008 Apr;43(4):375-87
references.pmid: 17850866
references.citation: Curr Biol. 2009 May 26;19(10):853-8
references.pmid: 19375314
references.citation: FASEB J. 2008 Mar;22(3):752-61
references.pmid: 17905723
references.citation: Biochem J. 2001 Aug 1;357(Pt 3):673-85
references.pmid: 11463338
references.citation: Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6295-9
references.pmid: 8392195
references.citation: J Biol Chem. 2008 May 9;283(19):12935-40
references.pmid: 18326500
references.citation: J Biol Chem. 2009 Mar 27;284(13):8421-6
references.pmid: 19189966
references.citation: Nat Cell Biol. 2009 Mar;11(3):337-43
references.pmid: 19182790
references.citation: J Biol Chem. 1989 Jul 25;264(21):12266-71
references.pmid: 2663854
references.citation: J Physiol. 2008 Jan 15;586(2):419-25
references.pmid: 18006576
references.citation: J Biol Chem. 2008 Feb 22;283(8):4622-31
references.pmid: 18156181
references.citation: Nature. 2005 Oct 6;437(7060):902-5
references.pmid: 16208375
references.citation: Soc Gen Physiol Ser. 1996;51:241-54
references.pmid: 8809948
references.citation: J Membr Biol. 1996 Mar;150(1):63-71
references.pmid: 8699480
references.citation: J Cell Biol. 1997 Sep 22;138(6):1333-41
references.pmid: 9298988
references.citation: Curr Biol. 2007 May 1;17(9):794-800
references.pmid: 17442569
references.citation: J Cell Biol. 1996 Aug;134(3):771-82
references.pmid: 8707854
references.citation: Genomics. 1996 Oct 15;37(2):253-6
references.pmid: 8921403
references.citation: Nature. 2008 Nov 6;456(7218):116-20
references.pmid: 18820677
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4682-7
references.pmid: 17360584
references.citation: Acta Pharmacol Sin. 2008 Jan;29(1):90-7
references.pmid: 18158870
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9479-84
references.pmid: 15194822
references.citation: J Biol Chem. 2008 Mar 21;283(12):8014-22
references.pmid: 18187424
references.citation: Nature. 1998 Apr 30;392(6679):936-41
references.pmid: 9582076
references.citation: Neuron. 2008 Sep 25;59(6):846-60
references.pmid: 18817726
references.citation: Biochem Biophys Res Commun. 2009 Jul 17;385(1):49-54
references.pmid: 19433061
references.citation: J Physiol. 2007 Mar 15;579(Pt 3):679-89
references.pmid: 17218358
references.citation: Mol Cell. 2008 Nov 7;32(3):439-48
references.pmid: 18995841
references.citation: Cell Calcium. 2007 Aug;42(2):163-72
references.pmid: 17499354
references.citation: Nat Cell Biol. 2009 Dec;11(12):1465-72
references.pmid: 19881501
references.citation: J Biol Chem. 2009 Apr 10;284(15):9733-41
references.pmid: 19228695
references.citation: J Biol Chem. 2007 Jun 1;282(22):16232-43
references.pmid: 17293345
references.citation: Curr Biol. 2009 Nov 3;19(20):1724-9
references.pmid: 19765994
references.citation: FASEB J. 1996 Nov;10(13):1505-17
references.pmid: 8940296
references.citation: Cell Calcium. 1986 Feb;7(1):1-12
references.pmid: 2420465
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3202-6
references.pmid: 19221033
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14687-92
references.pmid: 19706554
references.citation: J Gen Physiol. 1996 May;107(5):597-610
references.pmid: 8740373
references.citation: J Biol Chem. 2009 Jun 5;284(23):15903-15
references.pmid: 19366689
references.citation: Biochem J. 1989 Mar 1;258(2):409-12
references.pmid: 2650680
references.citation: Biochem Biophys Res Commun. 1996 Aug 23;225(3):777-84
references.pmid: 8780689
references.citation: Cell Calcium. 2010 Apr;47(4):350-9
references.pmid: 20172609
references.citation: J Cell Sci. 2007 Jun 15;120(Pt 12):1959-65
references.pmid: 17478524
references.citation: J Biol Chem. 2009 Sep 11;284(37):24933-8
references.pmid: 19622747
references.citation: Proc Natl Acad Sci U S A. 2007 May 29;104(22):9301-6
references.pmid: 17517596
references.citation: J Physiol. 2007 Mar 15;579(Pt 3):703-15
references.pmid: 17158173
references.citation: Nature. 2006 Sep 14;443(7108):230-3
references.pmid: 16921383
references.citation: J Biol Chem. 2008 Jun 20;283(25):17662-71
references.pmid: 18420579