Ca²⁺ Signaling in Cytoskeletal Reorganization, Cell Migration, and Cancer Metastasis

Figure 3

Internal Ca²⁺ storage is maintained through the differential activities of store-operated Ca²⁺ (SOC) influx during cell migration. Repetitive Ca²⁺ release from inositol triphosphate (IP₃) receptors causes the depletion of Ca²⁺ in the endoplasmic reticulum (ER) near the leading edge. Such Ca²⁺ depletion activates STIM1 (shown as ST in the illustration), which is translocated to the ER-plasma membrane junction to open Ca²⁺ channels ORAI1 (shown as O in the illustration). The inward Ca²⁺ current through ORAI1 will further travel into the ER via sarcoplasmic/endoplasmic reticular Ca²⁺-ATPase (SERCA, shown as SE in the illustration). In migrating cells, STIM1 proteins are enriched in the front ER to maintain Ca²⁺ homeostasis, which is essential for proper polarity and motility.