Figure 8.

Model to depict functional coupling between Stim1- and Orai1-mediating calcium entry. Stim1/Orai1-mediated calcium entry is critical for endothelial permeability via activation of calcium-sensitive PKCα. Within these ER-PM junctions, Ca²⁺ enters via Orai1 (the PM Ca²⁺ entry channel), where the channel interacts with Stim1 (the ER luminal Ca²⁺ sensor), and is activated. Ca²⁺ entry through Orai1 channel induces multiple signaling pathways such as activation of the NF-κB pathway [40]. The classical PKCα isoforms contains both calcium- and diacylglycerol-binding domains, and activation of PKCα is accompanied by translocation to the plasma membrane. ER – endoplasmic reticulum; PM – plasmic membrane; DAG – diacylglycerol.