Figure 8.

Resting and activated state of SOCE consisting of Ca²⁺ related ion channels in close proximity to or in complex with diverse accessory proteins. Under resting conditions with high Ca²⁺ concentrations in the ER, STIM1 and Orai1 remain in the quiescent state. In dependence of the cell type located in close proximity to TRPC1, CaV1.2, or interplay with adenylyl cyclase 8 (AC8) and/or SK3. Caveolin-1, proposed to interact with Orai1 as well as SK3 channel, is depicted in the inner face of the plasma membrane (left panel). Upon Ca²⁺ store depletion, CRAC channel complex formation is modulated by accessory modulators such as Golli, CRACR2A, Calmodulin, SARAF, and POST (right panel). Interaction of adenylyl cyclase to activated Orai1 triggers downstream signaling processes such as cAMP-PKA pathway [363] (not shown). CRAC channel complexes can form within caveolae. There, STIM1 potentially interacts with and activates TRPC1. Interaction of SK3 channel with accessory modulator SigmaR1 is known to support SK3 and Orai1 co-localization to promote Orai1-dependent SK3 channel activation as outlined in Section 9.