biostudies-literatureSassano MLStichting Tegen KankerEOS consortiumFonds Wetenschappelijk Onderzoek25152564211052392https://www.ebi.ac.uk/biostudies/studies/S-EPMC10243573biostudies-literatureUnknown4We recently reported that the ER stress kinase PERK regulates ER-mitochondria appositions and ER- plasma membrane (ER-PM) contact sites, independent of its canonical role in the unfolded protein response. PERK regulation of ER-PM contacts was revealed by a proximity biotinylation (BioID) approach and involved a dynamic PERK-Filamin A interaction supporting the formation of ER-PM contacts by actin-cytoskeleton remodeling in response to depletion of ER-Ca²⁺ stores. In this report, we further interrogated the PERK BioID interactome by validating through co-IP experiments the interaction between PERK and two proteins involved in Ca²⁺ handling and ER-mitochondria contact sites. These included the vesicle associated membrane (VAMP)-associated proteins (VAPA/B) and the main ER Ca²⁺ pump sarcoplasmic/endoplasmic reticulum Ca ATPase 2 (SERCA2). These data identify new putative PERK interacting proteins with a crucial role in membrane contact sites and Ca²⁺ signaling further supporting the uncanonical role of PERK in Ca²⁺ signaling through membrane contact sites (MCSs).Contact (Thousand Oaks (Ventura County, Calif.))Interactome Analysis of the ER Stress Sensor Perk Uncovers Key Components of ER-Mitochondria Contact Sites and Ca²⁺ Signalling.PMC10243573G076617N30837538FAF-F/2018/1252G049817NG070115NDerua RWaelkens Evan Vliet ARSassano MLAgostinis PfalseInteractome Analysis of the ER Stress Sensor Perk Uncovers Key Components of ER-Mitochondria Contact Sites and Ca²⁺ Signalling.We recently reported that the ER stress kinase PERK regulates ER-mitochondria appositions and ER- plasma membrane (ER-PM) contact sites, independent of its canonical role in the unfolded protein response. PERK regulation of ER-PM contacts was revealed by a proximity biotinylation (BioID) approach and involved a dynamic PERK-Filamin A interaction supporting the formation of ER-PM contacts by actin-cytoskeleton remodeling in response to depletion of ER-Ca²⁺ stores. In this report, we further interrogated the PERK BioID interactome by validating through co-IP experiments the interaction between PERK and two proteins involved in Ca²⁺ handling and ER-mitochondria contact sites. These included the vesicle associated membrane (VAMP)-associated proteins (VAPA/B) and the main ER Ca²⁺ pump sarcoplasmic/endoplasmic reticulum Ca ATPase 2 (SERCA2). These data identify new putative PERK interacting proteins with a crucial role in membrane contact sites and Ca²⁺ signaling further supporting the uncanonical role of PERK in Ca²⁺ signaling through membrane contact sites (MCSs).2021-01-01T00:00:00Z2021 Jan-Dec2025-04-04T20:28:37.76Z2025-02-19T03:19:30.666ZS-EPMC102435733736638010.1177/25152564211052392