Physiological and Pathophysiological Functions of SOCE in the Immune System

Overview

Journal Front Biosci (Elite Ed)

Specialty Biology

Date 2011 Dec 29

PMID 22202035

Citations 48

Authors

Patrick J Shaw

Stefan Feske

Affiliations

Soon will be listed here.

Abstract

Calcium signals play a critical role in many cell-type specific effector functions during innate and adaptive immune responses. The predominant mechanism to raise intracellular (Ca²⁺) used by most immune cells is store-operated Ca²⁺ entry (SOCE), whereby the depletion of endoplasmic reticulum (ER) Ca²⁺ stores triggers the influx of extracellular Ca²⁺. SOCE in immune cells is mediated by the highly Ca²⁺ selective Ca²⁺-release-activated Ca²⁺ (CRAC) channel, encoded by ORAI1, ORAI2 and ORAI3 genes. ORAI proteins are activated by stromal interaction molecules (STIM) 1 and 2, which act as sensors of ER Ca²⁺ store depletion. The importance of SOCE mediated by STIM and ORAI proteins for immune function is evident from the immunodeficiency and autoimmunity in patients with mutations in STIM1 and ORAI1 genes. These patients and studies in gene-targeted mice have revealed an essential role for ORAI/STIM proteins in the function of several immune cells. This review focuses on recent advances made towards understanding the role of SOCE in immune cells with an emphasis on the immune dysregulation that results from defects in SOCE in human patients and transgenic mice.

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References

Ko W, Chan H, Wong P . Anion secretion induced by capacitative Ca2+ entry through apical and basolateral membranes of cultured equine sweat gland epithelium. J Physiol. 1996; 497 ( Pt 1):19-29. PMC: 1160909. DOI: 10.1113/jphysiol.1996.sp021746. View

Brandman O, Liou J, Park W, Meyer T . STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels. Cell. 2007; 131(7):1327-39. PMC: 2680164. DOI: 10.1016/j.cell.2007.11.039. View

Vig M, Kinet J . Calcium signaling in immune cells. Nat Immunol. 2008; 10(1):21-7. PMC: 2877033. DOI: 10.1038/ni.f.220. View

Matsumoto M, Fujii Y, Baba A, Hikida M, Kurosaki T, Baba Y . The calcium sensors STIM1 and STIM2 control B cell regulatory function through interleukin-10 production. Immunity. 2011; 34(5):703-14. DOI: 10.1016/j.immuni.2011.03.016. View

Gwack Y, Srikanth S, Oh-Hora M, Hogan P, Lamperti E, Yamashita M . Hair loss and defective T- and B-cell function in mice lacking ORAI1. Mol Cell Biol. 2008; 28(17):5209-22. PMC: 2519726. DOI: 10.1128/MCB.00360-08. View

Schorr W, Swandulla D, Zeilhofer H . Mechanisms of IL-8-induced Ca2+ signaling in human neutrophil granulocytes. Eur J Immunol. 1999; 29(3):897-904. DOI: 10.1002/(SICI)1521-4141(199903)29:03<897::AID-IMMU897>3.0.CO;2-5. View

Sommers C, Park C, Lee J, Feng C, Fuller C, Grinberg A . A LAT mutation that inhibits T cell development yet induces lymphoproliferation. Science. 2002; 296(5575):2040-3. DOI: 10.1126/science.1069066. View

Negishi I, Motoyama N, Nakayama K, Senju S, Hatakeyama S, Zhang Q . Essential role for ZAP-70 in both positive and negative selection of thymocytes. Nature. 1995; 376(6539):435-8. DOI: 10.1038/376435a0. View

Feske S, Prakriya M, Rao A, Lewis R . A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients. J Exp Med. 2005; 202(5):651-62. PMC: 2212870. DOI: 10.1084/jem.20050687. View

10.

Kobayashi K, Takahashi K, Nagasawa S . The role of tyrosine phosphorylation and Ca2+ accumulation in Fc gamma-receptor-mediated phagocytosis of human neutrophils. J Biochem. 1995; 117(6):1156-61. DOI: 10.1093/oxfordjournals.jbchem.a124838. View

11.

Yeromin A, Zhang S, Jiang W, Yu Y, Safrina O, Cahalan M . Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai. Nature. 2006; 443(7108):226-9. PMC: 2756048. DOI: 10.1038/nature05108. View

12.

Smith H, Heusel J, Mehta I, Kim S, Dorner B, Naidenko O . Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc Natl Acad Sci U S A. 2002; 99(13):8826-31. PMC: 124383. DOI: 10.1073/pnas.092258599. View

13.

Dolmetsch R, Lewis R, Goodnow C, Healy J . Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature. 1997; 386(6627):855-8. DOI: 10.1038/386855a0. View

14.

Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y . TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med. 2008; 14(7):738-47. PMC: 2789807. DOI: 10.1038/nm1758. View

15.

Vig M, DeHaven W, Bird G, Billingsley J, Wang H, Rao P . Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store-operated calcium release-activated calcium channels. Nat Immunol. 2007; 9(1):89-96. PMC: 2377025. DOI: 10.1038/ni1550. View

16.

Smyth J, Hwang S, Tomita T, DeHaven W, Mercer J, Putney J . Activation and regulation of store-operated calcium entry. J Cell Mol Med. 2010; 14(10):2337-49. PMC: 3074973. DOI: 10.1111/j.1582-4934.2010.01168.x. View

17.

Zhou Y, Ramachandran S, Oh-Hora M, Rao A, Hogan P . Pore architecture of the ORAI1 store-operated calcium channel. Proc Natl Acad Sci U S A. 2010; 107(11):4896-901. PMC: 2841875. DOI: 10.1073/pnas.1001169107. View

18.

Partiseti M, Le Deist F, Hivroz C, Fischer A, Korn H, Choquet D . The calcium current activated by T cell receptor and store depletion in human lymphocytes is absent in a primary immunodeficiency. J Biol Chem. 1994; 269(51):32327-35. View

19.

Tapper H . The secretion of preformed granules by macrophages and neutrophils. J Leukoc Biol. 1996; 59(5):613-22. DOI: 10.1002/jlb.59.5.613. View

20.

Fu G, Chen Y, Yu M, Podd A, Schuman J, He Y . Phospholipase C{gamma}1 is essential for T cell development, activation, and tolerance. J Exp Med. 2010; 207(2):309-18. PMC: 2822604. DOI: 10.1084/jem.20090880. View