title: ER-luminal thiol/selenol-mediated regulation of Ca2+ signalling.
abstract: The endoplasmic reticulum (ER) is the main cellular Ca(2+)storage unit. Among other signalling outputs, the ER can release Ca(2+)ions, which can, for instance, communicate the status of ER protein folding to the cytosol and to other organelles, in particular the mitochondria. As a consequence, ER Ca(2+)flux can alter the apposition of the ER with mitochondria, influence mitochondrial ATP production or trigger apoptosis. All aspects of ER Ca(2+)flux have emerged as processes that are intimately controlled by intracellular redox conditions. In this review, we focus on ER-luminal redox-driven regulation of Ca(2+)flux. This involves the direct reduction of disulfides within ER Ca(2+)handling proteins themselves, but also the regulated interaction of ER chaperones and oxidoreductases such as calnexin or ERp57 with them. Well-characterized examples are the activating interactions of Ero1α with inositol 1,4,5-trisphosphate receptors (IP3Rs) or of selenoprotein N (SEPN1) with sarco/endoplasmic reticulum Ca(2+)transport ATPase 2 (SERCA2). The future discovery of novel ER-luminal modulators of Ca(2+)handling proteins is likely. Based on the currently available information, we describe how the variable ER redox conditions govern Ca(2+)flux from the ER.
authors.affiliation: Berufsfachschule Gesundheit Baselland, CH-4142 Münchenstein, Switzerland Thomas.Simmen@ualberta.ca christian.appenzeller@sbl.ch).
authors.forename: Christian
authors.initials: C
authors.lastname: Appenzeller-Herzog
authors.affiliation: Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G2H7 Thomas.Simmen@ualberta.ca christian.appenzeller@sbl.ch).
authors.forename: Thomas
authors.initials: T
authors.lastname: Simmen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020013:Calcium Signaling; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D010084:Oxidation-Reduction; D018036:Selenium Compounds / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D018832:Molecular Chaperones; D018036:Selenium Compounds; D013438:Sulfhydryl Compounds; C442270:selenol
keywords: 4; 5-trisphosphate receptor (IP3R); calcium; endoplasmic reticulum (ER); inositol 1; mitochondria-associated membrane (MAM); redox-dependent regulation; sarco/endoplasmic reticulum Ca2+ transport ATPase (SERCA); signal transduction