The AMPylase FIC-1 modulates TGF-β signaling in Caenorhabditis elegans

Mirella A Hernandez-Lima; Margaret Champion; Zachary Mattiola; Matthias C Truttmann

doi:10.3389/fnmol.2022.912734

The AMPylase FIC-1 modulates TGF-β signaling in Caenorhabditis elegans

Front Mol Neurosci. 2022 Nov 24:15:912734. doi: 10.3389/fnmol.2022.912734. eCollection 2022.

Authors

Mirella A Hernandez-Lima^{1

2}, Margaret Champion², Zachary Mattiola², Matthias C Truttmann^{1

2

3}

Affiliations

¹ Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, United States.
² Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, United States.
³ Geriatrics Center, University of Michigan, Ann Arbor, MI, United States.

Abstract

Post-translational protein modifications are essential for the spatio-temporal regulation of protein function. In this study, we examine how the activity of the Caenorhabditis elegans AMPylase FIC-1 modulates physiological processes in vivo. We find that over-expression (OE) of the constitutive AMPylase FIC-1(E274G) impairs C. elegans development, fertility, and stress resilience. We also show that FIC-1(E274G) OE inhibits pathogen avoidance behavior by selectively suppressing production of the Transforming Growth Factor-β (TGF-β) ligands DAF-7 and DBL-1 in ASI sensory neurons. Finally, we demonstrate that FIC-1 contributes to the regulation of adult body growth, cholinergic neuron function, and larval entry into dauer stage; all processes controlled by TGF-β signaling. Together, our results suggest a role for FIC-1 in regulating TGF-β signaling in C. elegans.

Keywords: AMPylation/adenylylation; FIC activity; chaperones; proteostasis; transforming growth factor.

Abstract

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