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bioRxiv · 10.1101/2021.04.16.440208

Deletion of the AMPylase mFICD alters cytokine secretion and affects cognitive plasticity in vivo

McCaul, N.·Porter, C. M.·Becker, A.·Tang, C.-H. A.·Wijne, C.·Chatterjee, B. K.·Bousbaine, D.·Bilate, A. M.·Hu, C.-C. A.·Ploegh, H. L.·Truttmann, M. C.
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Abstract

Fic domain-containing AMP transferases (fic AMPylases) are conserved enzymes that catalyze the covalent transfer of AMP to proteins. This post-translational modification regulates the function of several proteins, including the ER-resident chaperone Grp78/BiP. Here we introduce a mFICD AMPylase knock-out mouse model to study fic AMPylase function in vertebrates. We find that mFICD deficiency is well-tolerated in unstressed mice. We 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 and IL-1{beta}, without affecting the unfolded protein response. Finally, we demonstrate that older mFICD-/- mice show improved cognitive plasticity. Together, our results suggest a role for mFICD in adaptive immunity and neuronal plasticity in vivo.

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McCaul, N., Porter, C. M., Becker, A., Tang, C.-H. A., Wijne, C., Chatterjee, B. K., Bousbaine, D., Bilate, A. M., Hu, C.-C. A., Ploegh, H. L., Truttmann, M. C.. 2021-04-17. Deletion of the AMPylase mFICD alters cytokine secretion and affects cognitive plasticity in vivo. https://doi.org/10.1101/2021.04.16.440208

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