دورية أكاديمية
Selenoprotein N is an endoplasmic reticulum calcium sensor that links luminal calcium levels to a redox activity.
| العنوان: | Selenoprotein N is an endoplasmic reticulum calcium sensor that links luminal calcium levels to a redox activity. |
|---|---|
| المؤلفون: | Chernorudskiy A; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy., Varone E; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy., Colombo SF; Institute of Neuroscience, Consiglio Nazionale delle Ricerche and BIOMETRA Department, Università degli Studi di Milano, 20129 Milan, Italy., Fumagalli S; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy., Cagnotto A; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy., Cattaneo A; Proteomics/MS Facility, Cogentech SRL Benefit Corporation, 20139 Milan, Italy., Briens M; Architecture et Réactivité de l'ARN, CNRS, Université de Strasbourg, 67084 Strasbourg, France., Baltzinger M; Architecture et Réactivité de l'ARN, CNRS, Université de Strasbourg, 67084 Strasbourg, France., Kuhn L; Architecture et Réactivité de l'ARN, CNRS, Université de Strasbourg, 67084 Strasbourg, France., Bachi A; IFOM-FIRC Institute of Molecular Oncology, 20139 Milan, Italy., Berardi A; Biomolecular NMR Unit, IRCCS Ospedale S. Raffaele, 20132 Milan, Italy., Salmona M; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy., Musco G; Biomolecular NMR Unit, IRCCS Ospedale S. Raffaele, 20132 Milan, Italy., Borgese N; Institute of Neuroscience, Consiglio Nazionale delle Ricerche and BIOMETRA Department, Università degli Studi di Milano, 20129 Milan, Italy., Lescure A; Architecture et Réactivité de l'ARN, CNRS, Université de Strasbourg, 67084 Strasbourg, France., Zito E; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy; ester.zito@marionegri.it. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Sep 01; Vol. 117 (35), pp. 21288-21298. Date of Electronic Publication: 2020 Aug 17. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Calcium/*metabolism , Endoplasmic Reticulum/*metabolism , Intracellular Calcium-Sensing Proteins/*metabolism , Muscle Proteins/*metabolism , Selenoproteins/*metabolism, HeLa Cells ; Humans ; Intracellular Calcium-Sensing Proteins/genetics ; Muscle Proteins/genetics ; Oxidation-Reduction ; Selenoproteins/genetics |
| مستخلص: | The endoplasmic reticulum (ER) is the reservoir for calcium in cells. Luminal calcium levels are determined by calcium-sensing proteins that trigger calcium dynamics in response to calcium fluctuations. Here we report that Selenoprotein N (SEPN1) is a type II transmembrane protein that senses ER calcium fluctuations by binding this ion through a luminal EF-hand domain. In vitro and in vivo experiments show that via this domain, SEPN1 responds to diminished luminal calcium levels, dynamically changing its oligomeric state and enhancing its redox-dependent interaction with cellular partners, including the ER calcium pump sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). Importantly, single amino acid substitutions in the EF-hand domain of SEPN1 identified as clinical variations are shown to impair its calcium-binding and calcium-dependent structural changes, suggesting a key role of the EF-hand domain in SEPN1 function. In conclusion, SEPN1 is a ER calcium sensor that responds to luminal calcium depletion, changing its oligomeric state and acting as a reductase to refill ER calcium stores. Competing Interests: The authors declare no competing interest. (Copyright © 2020 the Author(s). Published by PNAS.) |
| References: | J Mol Biol. 2017 Mar 10;429(5):620-632. (PMID: 28137421) Cell Calcium. 2005 Sep-Oct;38(3-4):303-10. (PMID: 16076486) Redox Biol. 2019 Jun;24:101176. (PMID: 30921636) Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6055-E6063. (PMID: 27694578) Sci Rep. 2017 Jan 20;7:40993. (PMID: 28106121) Nat Rev Mol Cell Biol. 2000 Oct;1(1):11-21. (PMID: 11413485) Redox Biol. 2019 Jan;20:354-366. (PMID: 30391828) Trends Biochem Sci. 2018 Jan;43(1):32-43. (PMID: 29153511) Biopolymers. 2008 May;89(5):392-400. (PMID: 17896349) Yale J Biol Med. 1952 Dec;25(3):176-201. (PMID: 13015950) Anal Chem. 2003 Feb 1;75(3):663-70. (PMID: 12585499) Annu Rev Biochem. 1989;58:951-98. (PMID: 2673026) J Cell Biol. 2009 Sep 21;186(6):783-92. (PMID: 19752026) J Cell Biol. 2004 Jan 5;164(1):35-46. (PMID: 14699087) Sci Rep. 2013;3:1895. (PMID: 23719418) Antioxid Redox Signal. 2020 Apr 20;32(12):873-883. (PMID: 31825235) Cold Spring Harb Perspect Biol. 2011 May 01;3(5):. (PMID: 21441596) Nat Genet. 2001 Sep;29(1):17-8. (PMID: 11528383) J Cell Biol. 2015 Oct 26;211(2):253-9. (PMID: 26504166) J Cell Biol. 2005 May 9;169(3):435-45. (PMID: 15866891) Hum Mol Genet. 2003 May 1;12(9):1045-53. (PMID: 12700173) Curr Biol. 2005 Jul 12;15(13):1235-41. (PMID: 16005298) Science. 2011 Nov 25;334(6059):1081-6. (PMID: 22116877) Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16098-103. (PMID: 21896730) J Mol Biol. 2015 Jan 16;427(1):31-53. (PMID: 25134758) Nat Rev Mol Cell Biol. 2016 Feb;17(2):69-82. (PMID: 26627931) Nature. 2005 Oct 6;437(7060):902-5. (PMID: 16208375) Mol Cell. 2017 Jun 15;66(6):780-788. (PMID: 28622523) Protein Eng. 1993 Jun;6(4):383-90. (PMID: 8332596) J Cell Biol. 2013 Apr 15;201(2):337-49. (PMID: 23589496) J Biol Chem. 1999 Dec 31;274(53):38147-54. (PMID: 10608886) Hum Mol Genet. 2015 Apr 1;24(7):1843-55. (PMID: 25452428) Cell. 2005 Jan 14;120(1):85-98. (PMID: 15652484) |
| فهرسة مساهمة: | Keywords: SEPN1; calcium sensor; endoplasmic reticulum; stress of the endoplasmic reticulum |
| المشرفين على المادة: | 0 (Intracellular Calcium-Sensing Proteins) 0 (Muscle Proteins) 0 (SELENON protein, human) 0 (Selenoproteins) SY7Q814VUP (Calcium) |
| تواريخ الأحداث: | Date Created: 20200821 Date Completed: 20201023 Latest Revision: 20210111 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC7474598 |
| DOI: | 10.1073/pnas.2003847117 |
| PMID: | 32817544 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
|---|---|
| DOI: | 10.1073/pnas.2003847117 |