title: When under pressure, get closer: PERKing up membrane contact sites during ER stress.
abstract: The endoplasmic reticulum (ER) is the main hub of cellular Ca(2+)signalling and protein synthesis and folding. The ER moreover is the central player in the formation of contact sites with other organelles and structures, including mitochondria, plasma membrane (PM) and endosomes. The most studied of these, the ER-mitochondria contact sites, are crucial regulators of cellular Ca(2+)homoeostasis, metabolism and cell death signalling. Protein kinase RNA-like ER kinase (PERK), an ER stress kinase and crucial signalling protein in the unfolded protein response (UPR), was found to be able to orchestrate contact sites between the ER and mitochondria and to be indispensable for the pre-apoptotic trafficking of calreticulin (CRT) at the PM during immunogenic cell death (ICD). Furthermore, PERK has recently been linked with ER and PM contact sites through the mechanism of store-operated Ca(2+)entry (SOCE). Here we discuss emerging findings disclosing novel roles of the ER stress sensor PERK in orchestrating inter-organellar communication in the context of ER stress.
authors.affiliation: Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven B-3000, Belgium.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: van Vliet
authors.affiliation: Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven B-3000, Belgium Patrizia.Agostinis@med.kuleuven.be.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agostinis
mesh_terms: D000818:Animals; D001665:Binding Sites; D037282:Calreticulin / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: D037282:Calreticulin
keywords: MAMs; endoplasmic reticulum; mitochondria; plasma membrane; protein kinase RNA-like ER kinase (PERK); store operated Ca2+ entry (SOCE)