Schematic illustrating mechanism of endothelial cell calcium signaling during TEM. The endothelial cell calcium signaling pathway is activated by homophilic PECAM–PECAM interactions. This leads to activation of TRPC6 and an influx of calcium. The CHD helps enrich IQGAP1 at the junction, allowing CaM bound to the IQ domain to be locally concentrated for the calcium influx. The local influx of calcium allows CaM to then activate CaMKIIδ. CaMKIIδ subsequently mediates targeted delivery of the LBRC to facilitate TEM. Note that CaMKII is shown as a monomer for clarity.