@article{f6a7f781aa9d49a9acce6787d34ad035,
title = "Deletion of mFICD AMPylase alters cytokine secretion and affects visual short-term learning in vivo",
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.",
keywords = "posttranslational modification, AMPylation, FICD, HYPE, BiP, UPR",
author = "Nicholas McCaul and Porter, {Corey M.} and Anouk Becker and Tang, {Chih Hang Anthony} and Charlotte Wijne and Bhaskar Chatterjee and Djenet Bousbaine and Angelina Bilate and Hu, {Chih Chi Andrew} and Hidde Ploegh and Truttmann, {Matthias C.}",
note = "Funding Information: This work was supported by grants NIH/NCI R01CA163910 to C.-C. A. H. and support from AARG and MICHR UL1TR002240 to M. C. T. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: Funding and additional information—This work was supported by grants NIH/NCI R01CA163910 to C.-C. A. H. and support from AARG and MICHR UL1TR002240 to M. C. T. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2021 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).",
year = "2021",
month = sep,
day = "1",
doi = "10.1016/j.jbc.2021.100991",
language = "English",
volume = "297",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",
}
