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Deletion of mFICD AMPylase alters cytokine secretion and affects visual short-term learning in vivo.

Authors
  • McCaul, Nicholas1
  • Porter, Corey M2
  • Becker, Anouk3
  • Tang, Chih-Hang Anthony4
  • Wijne, Charlotte3
  • Chatterjee, Bhaskar2
  • Bousbaine, Djenet5
  • Bilate, Angelina3
  • Hu, Chih-Chi Andrew4
  • Ploegh, Hidde6
  • Truttmann, Matthias C7
  • 1 Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, USA; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
  • 2 Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
  • 3 Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
  • 4 Center for Translational Research in Hematologic Malignancies, Houston Methodist Cancer Center, Houston Methodist Research Institute, Houston, Texas, USA. , (Mali)
  • 5 Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, USA; Microbiology Graduate Program, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • 6 Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, USA. Electronic address: [email protected]
  • 7 Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA; Geriatrics Center, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: [email protected]
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry and Molecular Biology
Publication Date
Aug 19, 2021
Volume
297
Issue
3
Pages
100991–100991
Identifiers
DOI: 10.1016/j.jbc.2021.100991
PMID: 34419450
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Fic domain-containing AMP transferases (fic AMPylases) are conserved enzymes that catalyze the covalent transfer of AMP to proteins. This posttranslational modification regulates the function of several proteins, including the ER-resident chaperone Grp78/BiP. Here we introduce a mouse FICD (mFICD) AMPylase knockout mouse model to study fic AMPylase function in vertebrates. We find that mFICD deficiency is well tolerated in unstressed mice. We also show that mFICD-deficient mouse embryonic fibroblasts are depleted of AMPylated proteins. mFICD deletion alters protein synthesis and secretion in splenocytes, including that of IgM, an antibody secreted early during infections, and the proinflammatory cytokine IL-1β, without affecting the unfolded protein response. Finally, we demonstrate that visual nonspatial short-term learning is stronger in old mFICD-/- mice than in wild-type controls while other measures of cognition, memory, and learning are unaffected. Together, our results suggest a role for mFICD in adaptive immunity and neuronal plasticity in vivo. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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