Store-operated calcium entry pathway (SOCE) (SOCE)

The store-operated calcium entry (SOCE) pathway is a fundamental cellular mechanism for regulating calcium influx in response to the depletion of intracellular calcium stores, primarily the endoplasmic reticulum (ER) (UniProt, PubMed). The core components of this pathway are the ER-resident calcium sensor, stromal interaction molecule 1 (STIM1), and the plasma membrane-localized calcium channel, Orai1 (NIH, Frontiers). Upon sensing a drop in ER calcium levels, STIM1 undergoes a conformational change, oligomerizes, and translocates to junctions between the ER and the plasma membrane (J Biol Chem). At these sites, STIM1 directly interacts with and activates Orai1 channels, as well as certain transient receptor potential (TRP) channels, to facilitate a sustained influx of extracellular calcium (NIH, PubMed). This calcium signal is essential for numerous physiological processes, including T-cell activation, cytokine production, platelet aggregation, and muscle contraction (Frontiers, NIH). Dysregulation of the SOCE pathway is implicated in a wide range of diseases, such as severe combined immunodeficiency, autoimmunity, cancer progression, and inflammatory disorders like acute pancreatitis (PubMed, NIH). Consequently, the SOCE pathway has emerged as a promising therapeutic target, with several small-molecule inhibitors like CM4620 currently in clinical development for treating inflammatory and autoimmune conditions (CalciMedica, PubMed).

Other names

CRAC channel pathwaySTIM1-Orai1 complexStore-operated calcium channel (SOCC)Calcium release-activated calcium channel pathwaySTIM-Orai pathwayIcrac pathway

Inhibition of store-operated calcium entry by blocking Orai1 channels or disrupting the STIM1-Orai1 interaction.