PERKs of plasma membrane–ER communication

PRKR-like endoplasmic reticulum kinase (PERK) is an ER protein that regulates the unfolded protein response, but it has also been implicated in other cellular processes, including calcium (Ca²⁺) signalling. van Vliet et al. identified actin regulators as important PERK interactors in mammalian cells. Knockout of Perk in mouse embryonic fibroblasts results in abnormal accumulation of filamentous actin (F-actin) at the cell cortex. Depletion of ER Ca²⁺ stores (or increase in cytosolic Ca²⁺) normally induces the formation of plasma membrane–ER contact sites, which promote transport of Ca²⁺ to the ER. However, the cortical F-actin accumulations in Perk^−/− cells interfered with the establishment of these contact sites, indicating that PERK — through its involvement in modulating actin organization — has an important function in regulating plasma membrane–ER contact site formation and Ca²⁺ homeostasis.