title: Store-operated CRAC channels: function in health and disease.
abstract: Elevation of cytosolic Ca(2+) levels through the activation of store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels is involved in mediating a disparate array of cellular responses. These include secretion, metabolism and gene expression, as well as cell growth and proliferation. Moreover, emerging evidence points to the involvement of aberrant CRAC channel activity in human diseases, such as certain types of immunodeficiency and autoimmunity disorders, allergy, and inflammatory bowel disease. This article summarizes recent advances in understanding the gating and function of CRAC channels, their links to human disease and key issues for the development of channel blockers.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK. anant.parekh@dpag.ox.ac.uk
authors.forename: Anant B
authors.initials: AB
authors.lastname: Parekh
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation; D016503:Drug Delivery Systems; D015195:Drug Design; D005786:Gene Expression Regulation; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy / Q000503:physiopathology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002118:Calcium
references.citation: Curr Biol. 2007 May 1;17(9):794-800
references.pmid: 17442569
references.citation: FASEB J. 2009 Mar;23(3):894-905
references.pmid: 18978154
references.citation: Cancer Cell. 2009 Feb 3;15(2):124-34
references.pmid: 19185847
references.citation: Cell Calcium. 2002 Nov-Dec;32(5-6):269-78
references.pmid: 12543089
references.citation: Mol Cell Biol. 2008 Sep;28(17):5209-22
references.pmid: 18591248
references.citation: Physiol Rev. 2005 Apr;85(2):757-810
references.pmid: 15788710
references.citation: Clin Exp Allergy. 2006 Jun;36(6):689-703
references.pmid: 16776669
references.citation: Nature. 1998 Apr 30;392(6679):933-6
references.pmid: 9582075
references.citation: J Exp Med. 2005 Sep 5;202(5):651-62
references.pmid: 16147976
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: Mol Pharmacol. 2006 Apr;69(4):1413-20
references.pmid: 16407466
references.citation: Nature. 2006 Sep 14;443(7108):226-9
references.pmid: 16921385
references.citation: J Biol Chem. 2004 Mar 26;279(13):12427-37
references.pmid: 14718545
references.citation: Nat Immunol. 2008 Jan;9(1):89-96
references.pmid: 18059270
references.citation: J Allergy Clin Immunol. 1999 Jul;104(1):79-84
references.pmid: 10400843
references.citation: Clin Cancer Res. 2001 Jun;7(6):1600-9
references.pmid: 11410496
references.citation: Cell Calcium. 2002 Nov-Dec;32(5-6):379-91
references.pmid: 12543097
references.citation: J Biol Chem. 1994 Dec 23;269(51):32327-35
references.pmid: 7798233
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 Sep 11;284(37):24767-72
references.pmid: 19584058
references.citation: Cell. 2007 Dec 14;131(6):1047-58
references.pmid: 18083096
references.citation: Curr Allergy Asthma Rep. 2004 May;4(3):217-23
references.pmid: 15056404
references.citation: Nat Cell Biol. 2006 Jul;8(7):771-3
references.pmid: 16733527
references.citation: Am J Respir Cell Mol Biol. 2008 Jun;38(6):744-9
references.pmid: 18239188
references.citation: EMBO J. 2000 Dec 1;19(23):6401-7
references.pmid: 11101513
references.citation: Nat Immunol. 2006 Jan;7(1):25-32
references.pmid: 16357855
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4040-5
references.pmid: 16537481
references.citation: J Allergy Clin Immunol. 2009 Dec;124(6):1311-1318.e7
references.pmid: 20004786
references.citation: J Cell Biol. 2006 Sep 11;174(6):803-13
references.pmid: 16966422
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22516-21
references.pmid: 20018736
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: Biochem Biophys Res Commun. 2006 Dec 1;350(4):969-76
references.pmid: 17045966
references.citation: Pflugers Arch. 1995 Jul;430(3):315-22
references.pmid: 7491254
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10607-12
references.pmid: 10973476
references.citation: Cell. 2007 Dec 28;131(7):1327-39
references.pmid: 18160041
references.citation: Nature. 2008 Jul 24;454(7203):538-42
references.pmid: 18596693
references.citation: Lancet. 1991 Nov 16;338(8777):1238-9
references.pmid: 1682646
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: Neuron. 1998 Mar;20(3):389-99
references.pmid: 9539117
references.citation: Nat Cell Biol. 2008 Jun;10(6):688-97
references.pmid: 18488020
references.citation: Nat Cell Biol. 2006 Jul;8(7):655-6
references.pmid: 16820776
references.citation: Mol Endocrinol. 1997 Mar;11(3):281-91
references.pmid: 9058375
references.citation: Cell Calcium. 2007 Aug;42(2):145-56
references.pmid: 17572487
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: J Laryngol Otol. 2003 Jan;117(1):1-9
references.pmid: 12590849
references.citation: J Med Chem. 2000 Aug 10;43(16):2975-81
references.pmid: 10956206
references.citation: J Clin Oncol. 2003 Dec 1;21(23):4356-63
references.pmid: 14645425
references.citation: J Biol Chem. 2008 Nov 14;283(46):31348-55
references.pmid: 18806259
references.citation: J Allergy Clin Immunol. 2009 Nov;124(5):1014-21.e1-3
references.pmid: 19895990
references.citation: J Biol Chem. 2006 Jul 28;281(30):20661-20665
references.pmid: 16766533
references.citation: J Biol Chem. 2008 Jul 18;283(29):20261-7
references.pmid: 18499656
references.citation: Immunol Rev. 2009 Sep;231(1):189-209
references.pmid: 19754898
references.citation: Cell. 1997 Jan 10;88(1):49-55
references.pmid: 9019404
references.citation: Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1115-22
references.pmid: 11830654
references.citation: Nature. 1993 Nov 11;366(6451):158-61
references.pmid: 8232554
references.citation: J Gen Physiol. 2004 Feb;123(2):167-82
references.pmid: 14744989
references.citation: J Physiol. 2008 Jul 1;586(13):3043-54
references.pmid: 18467365
references.citation: Nat Rev Neurosci. 2001 Jun;2(6):387-96
references.pmid: 11389472
references.citation: J Physiol. 2008 Nov 15;586(22):5383-401
references.pmid: 18832420
references.citation: J Physiol. 2000 Jan 15;522 Pt 2:247-57
references.pmid: 10639101
references.citation: Physiol Rev. 2006 Jan;86(1):369-408
references.pmid: 16371601
references.citation: N Engl J Med. 2009 May 7;360(19):1971-80
references.pmid: 19420366
references.citation: EMBO J. 2002 Dec 16;21(24):6744-54
references.pmid: 12485995
references.citation: Cell Calcium. 2007 Aug;42(2):123-32
references.pmid: 17382385
references.citation: J Biol Chem. 2005 Mar 25;280(12):10997-1006
references.pmid: 15647288
references.citation: J Cell Biol. 2005 May 9;169(3):435-45
references.pmid: 15866891
references.citation: Physiol Rev. 2007 Jul;87(3):965-1010
references.pmid: 17615394
references.citation: J Biol Chem. 2004 Jul 16;279(29):29994-9
references.pmid: 15133023
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: Curr Opin Allergy Clin Immunol. 2003 Feb;3(1):1-6
references.pmid: 12582307
references.citation: Blood. 1995 Feb 15;85(4):1053-62
references.pmid: 7531512
references.citation: J Physiol. 2004 May 1;556(Pt 3):805-17
references.pmid: 14966303
references.citation: J Biol Chem. 2004 Feb 13;279(7):5641-7
references.pmid: 14585840
references.citation: J Biol Chem. 2007 Jul 6;282(27):19375-84
references.pmid: 17463004
references.citation: Curr Biol. 2005 Jul 12;15(13):1235-41
references.pmid: 16005298
references.citation: Physiol Rev. 2007 Jan;87(1):165-217
references.pmid: 17237345
references.citation: J Biol Chem. 2001 Dec 21;276(51):48118-26
references.pmid: 11592964
references.citation: Nat Cell Biol. 2009 Jun;11(6):669-77
references.pmid: 19488056
references.citation: J Exp Med. 2008 Jul 7;205(7):1583-91
references.pmid: 18559454
references.citation: Channels (Austin). 2009 Mar-Apr;3(2):129-39
references.pmid: 19411837
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9357-62
references.pmid: 16751269
references.citation: Eur J Pharmacol. 2007 Apr 10;560(2-3):225-33
references.pmid: 17307161
references.citation: Curr Biol. 2009 May 26;19(10):853-8
references.pmid: 19375314
references.citation: Mol Interv. 2001 Jun;1(2):84-94
references.pmid: 14993328
references.citation: J Physiol. 1993 Jun;465:359-86
references.pmid: 8229840
references.citation: Nat Cell Biol. 2009 Apr;11(4):433-42
references.pmid: 19287379
references.citation: Oncogene. 2003 Nov 24;22(53):8619-27
references.pmid: 14634623
references.citation: Nature. 1993 Jan 28;361(6410):315-25
references.pmid: 8381210
references.citation: FASEB J. 2008 Mar;22(3):752-61
references.pmid: 17905723
references.citation: Nat Rev Mol Cell Biol. 2003 Jul;4(7):517-29
references.pmid: 12838335
references.citation: Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6295-9
references.pmid: 8392195
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: Nature. 2007 Mar 15;446(7133):284-7
references.pmid: 17361175
references.citation: J Physiol. 2008 Jan 15;586(2):419-25
references.pmid: 18006576
references.citation: Science. 1992 Oct 9;258(5080):307-10
references.pmid: 1384130
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: Cancer Cell. 2002 Mar;1(2):169-79
references.pmid: 12086875
references.citation: Cell Death Differ. 2007 Jul;14(7):1295-304
references.pmid: 17479110
references.citation: Nature. 2008 Nov 6;456(7218):116-20
references.pmid: 18820677
references.citation: Biochem Biophys Res Commun. 2009 Jul 17;385(1):49-54
references.pmid: 19433061
references.citation: Cell Calcium. 2008 Jul;44(1):6-13
references.pmid: 18243304
references.citation: Cell Calcium. 2007 Aug;42(2):111-21
references.pmid: 17445883
references.citation: J Cell Sci. 2005 Dec 1;118(Pt 23):5615-23
references.pmid: 16306224
references.citation: J Immunol. 2009 Sep 1;183(5):3454-62
references.pmid: 19648266
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: Cell Calcium. 1986 Feb;7(1):1-12
references.pmid: 2420465
references.citation: Nature. 2007 Nov 15;450(7168):376-82
references.pmid: 18004376
references.citation: Gastroenterology. 1998 Jul;115(1):182-205
references.pmid: 9649475
references.citation: Eur J Immunol. 1996 Sep;26(9):2119-26
references.pmid: 8814256
references.citation: J Gen Physiol. 1996 May;107(5):597-610
references.pmid: 8740373
references.citation: FASEB J. 2006 Nov;20(13):2381-3
references.pmid: 17023391
references.citation: Pflugers Arch. 1994 Oct;428(5-6):433-8
references.pmid: 7838664
references.citation: J Immunol. 2003 May 1;170(9):4441-9
references.pmid: 12707319
references.citation: Nat Immunol. 2008 Jan;9(1):81-8
references.pmid: 18059272
references.citation: Mol Pharmacol. 2004 Sep;66(3):702-7
references.pmid: 15322263
references.citation: Pflugers Arch. 2002 Mar;443(5-6):892-902
references.pmid: 11889590
references.citation: Proc Natl Acad Sci U S A. 2007 May 29;104(22):9301-6
references.pmid: 17517596
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
references.citation: Pulm Pharmacol Ther. 2008;21(2):360-9
references.pmid: 17977764