FIGURE 8.

Model depicting the effects of E2 on SOCE in airway epithelia. A, model of SOCE after ER Ca²⁺ depletion in the absence of E2. Phosphorylated STIM1 oligomerizes and interacts with Orai1 to induce SOCE. Elevations in cytoplasmic Ca²⁺ then lead to activation of CaCC. B, proposed model of E2/ESR1-mediated inhibition of STIM1 and SOCE after ER Ca²⁺ depletion. E2/ESR1 inhibits STIM1 phosphorylation via an unknown mechanism. This inhibits STIM1 oligomerization, redistribution, and interaction with Orai1 to block SOCE. Low cytoplasmic Ca²⁺ reduces CaCC activation.