Molecular Pharmacology of Store-operated CRAC Channels

Overview

Journal Channels (Austin)

Specialty Biochemistry

Date 2013 Jun 29

PMID 23807116

Citations 47

Authors

Amit Jairaman

Murali Prakriya

Affiliations

Soon will be listed here.

Abstract

Calcium influx through store-operated Ca(2+) release-activated Ca(2+) channels (CRAC channels) is a well-defined mechanism of generating cellular Ca(2+) elevations that regulates many functions including gene expression, exocytosis and cell proliferation. The identifications of the ER Ca(2+) sensing proteins, STIM1-2 and the CRAC channel proteins, Orai1-3, have led to improved understanding of the physiological roles and the activation mechanism of CRAC channels. Defects in CRAC channel function are associated with serious human diseases such as immunodeficiency and auto-immunity. In this review, we discuss several pharmacological modulators of CRAC channels, focusing specifically on the molecular mechanism of drug action and their utility in illuminating the mechanism of CRAC channel operation and their physiological roles in different cells.

Citing Articles

Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome.

de Araujo E, Tallo F, Oliveira A, Toghlobi G, Arantes R, Balsimelli R Biomedicines. 2024; 12(3).

PMID: 38540195 PMC: 10968603. DOI: 10.3390/biomedicines12030582.

Side-by-side comparison of published small molecule inhibitors against thapsigargin-induced store-operated Ca2+ entry in HEK293 cells.

Norman K, Hemmings K, Shawer H, Appleby H, Burnett A, Hamzah N PLoS One. 2024; 19(1):e0296065.

PMID: 38261554 PMC: 10805320. DOI: 10.1371/journal.pone.0296065.

The Ca channel ORAI1 is a regulator of oral cancer growth and nociceptive pain.

Son G, Tu N, Santi M, Loya Lopez S, Souza Bomfim G, Vinu M Sci Signal. 2023; 16(801):eadf9535.

PMID: 37669398 PMC: 10747475. DOI: 10.1126/scisignal.adf9535.

Store-Operated Ca Entry as a Putative Target of Flecainide for the Treatment of Arrhythmogenic Cardiomyopathy.

Moccia F, Brunetti V, Soda T, Faris P, Scarpellino G, Berra-Romani R J Clin Med. 2023; 12(16).

PMID: 37629337 PMC: 10455538. DOI: 10.3390/jcm12165295.

ORAI Calcium Channels: Regulation, Function, Pharmacology, and Therapeutic Targets.

Rubaiy H Pharmaceuticals (Basel). 2023; 16(2).

PMID: 37259313 PMC: 9967976. DOI: 10.3390/ph16020162.

References

Hoth M, Penner R . Calcium release-activated calcium current in rat mast cells. J Physiol. 1993; 465:359-86. PMC: 1175434. DOI: 10.1113/jphysiol.1993.sp019681. View

Yang S, Zhang J, Huang X . Orai1 and STIM1 are critical for breast tumor cell migration and metastasis. Cancer Cell. 2009; 15(2):124-34. DOI: 10.1016/j.ccr.2008.12.019. View

Li J, McKeown L, Ojelabi O, Stacey M, Foster R, ORegan D . Nanomolar potency and selectivity of a Ca²⁺ release-activated Ca²⁺ channel inhibitor against store-operated Ca²⁺ entry and migration of vascular smooth muscle cells. Br J Pharmacol. 2011; 164(2):382-93. PMC: 3174418. DOI: 10.1111/j.1476-5381.2011.01368.x. View

Li Z, Lu J, Xu P, Xie X, Chen L, Xu T . Mapping the interacting domains of STIM1 and Orai1 in Ca2+ release-activated Ca2+ channel activation. J Biol Chem. 2007; 282(40):29448-56. DOI: 10.1074/jbc.M703573200. View

Parekh A . Slow feedback inhibition of calcium release-activated calcium current by calcium entry. J Biol Chem. 1998; 273(24):14925-32. DOI: 10.1074/jbc.273.24.14925. View

Takezawa R, Cheng H, Beck A, Ishikawa J, Launay P, Kubota H . A pyrazole derivative potently inhibits lymphocyte Ca2+ influx and cytokine production by facilitating transient receptor potential melastatin 4 channel activity. Mol Pharmacol. 2006; 69(4):1413-20. DOI: 10.1124/mol.105.021154. View

Parekh A, Putney Jr J . Store-operated calcium channels. Physiol Rev. 2005; 85(2):757-810. DOI: 10.1152/physrev.00057.2003. View

Honnappa S, Montenegro Gouveia S, Weisbrich A, Damberger F, Bhavesh N, Jawhari H . An EB1-binding motif acts as a microtubule tip localization signal. Cell. 2009; 138(2):366-76. DOI: 10.1016/j.cell.2009.04.065. 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.

Ji W, Xu P, Li Z, Lu J, Liu L, Zhan Y . Functional stoichiometry of the unitary calcium-release-activated calcium channel. Proc Natl Acad Sci U S A. 2008; 105(36):13668-73. PMC: 2533247. DOI: 10.1073/pnas.0806499105. View

11.

Putney Jr J . The enigmatic TRPCs: multifunctional cation channels. Trends Cell Biol. 2004; 14(6):282-6. DOI: 10.1016/j.tcb.2004.04.002. View

12.

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

13.

Srikanth S, Jung H, Kim K, Souda P, Whitelegge J, Gwack Y . A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that stabilizes CRAC channels in T cells. Nat Cell Biol. 2010; 12(5):436-46. PMC: 2875865. DOI: 10.1038/ncb2045. View

14.

Fierro L, Parekh A . Fast calcium-dependent inactivation of calcium release-activated calcium current (CRAC) in RBL-1 cells. J Membr Biol. 1999; 168(1):9-17. DOI: 10.1007/s002329900493. View

15.

Owsianik G, Dhoedt D, Voets T, Nilius B . Structure-function relationship of the TRP channel superfamily. Rev Physiol Biochem Pharmacol. 2006; 156:61-90. View

16.

Zitt C, Strauss B, Schwarz E, Spaeth N, Rast G, Hatzelmann A . Potent inhibition of Ca2+ release-activated Ca2+ channels and T-lymphocyte activation by the pyrazole derivative BTP2. J Biol Chem. 2004; 279(13):12427-37. DOI: 10.1074/jbc.M309297200. View

17.

Putney J . Pharmacology of store-operated calcium channels. Mol Interv. 2010; 10(4):209-18. PMC: 2965610. DOI: 10.1124/mi.10.4.4. View

18.

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

19.

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

20.

Spinelli A, Gonzalez-Cobos J, Zhang X, Motiani R, Rowan S, Zhang W . Airway smooth muscle STIM1 and Orai1 are upregulated in asthmatic mice and mediate PDGF-activated SOCE, CRAC currents, proliferation, and migration. Pflugers Arch. 2012; 464(5):481-92. PMC: 3489062. DOI: 10.1007/s00424-012-1160-5. View