Figure 2.

Schematic describing the formation of ER- plasma membrane (PM) contact sites and the UPR. PERK dimerizes in response to calcium depletion in the ER lumen. The PERK dimer binds to filamin A (FLNA), followed by accelerating F-actin remodeling and formation of ER-PM contact sites containing stromal-interacting molecule 1 (STIM1) and Orai1. The contact sites promote calcium influx, which restores the calcium level to a normal value in the ER lumen. The IRE1 dimer also interacts with FLNA. Although the effect of the IRE1-FLNA interaction on the formation of ER-PM contact sites remains unclear, the binding of IRE1 to FLNA does modulate ER dynamics and cell migration.