Calcium release-activated calcium channel (CRAC channel) (CRAC channel)

Store-operated calcium entry (SOCE) channels, specifically the calcium release-activated calcium (CRAC) channels, are the primary route for calcium influx in mast cells and basophils following antigen stimulation (Parekh & Putney, 2005, Physiol Rev). These channels are formed by the interaction of the endoplasmic reticulum (ER) calcium sensor STIM1 and the plasma membrane pore-forming protein Orai1 (Vig & Kinet, 2009, Nat Immunol). When IgE-mediated signaling triggers the depletion of ER calcium stores, STIM1 undergoes a conformational change and translocates to the plasma membrane to activate Orai1, leading to a sustained increase in cytosolic calcium (Hogan et al., 2010, Nat Immunol). This calcium signal is indispensable for the degranulation process, which releases histamine and proteases, as well as the de novo synthesis of leukotrienes and pro-inflammatory cytokines (Di Capite et al., 2011, Curr Opin Allergy Clin Immunol). Consequently, CRAC channels are considered high-priority therapeutic targets for allergic and inflammatory diseases such as asthma and chronic urticaria (Zhang et al., 2020, Front Immunol). Pharmacological inhibition of these channels aims to suppress the hyper-responsiveness of mast cells and basophils, thereby reducing the severity of allergic reactions.

Other names

Store-operated calcium channelSOCE channelOrai1/STIM1 complexCalcium release-activated calcium channel protein 1Orai1STIM1

Inhibition of the Orai1 pore-forming subunit or disruption of the STIM1-Orai1 interaction to prevent store-operated calcium entry (SOCE).