From Young to Old: AMPylation Hits the Brain

Protein post-translational modifications (PTMs) are implicated in numerous physiological processes and significantly contribute to complex regulatory networks of protein functions. Recently, a protein PTM called AMPylation was found to play a role in modulation of neurodevelopment and neurodegeneration. Combination of biochemical and chemical proteomic studies has uncovered the prevalence of this PTM in regulation of diverse metabolic pathways. In metazoans, thus far two protein AMP transferases have been identified to introduce AMPylation: FICD and SELO. These two proteins were found to be involved in unfolded protein response and redox homeostasis on the cellular level and in the case of FICD to adjust the development of glial cells and neurons in Drosophila and cerebral organoids, respectively. Together with findings on AMPylation and its association with toxic protein aggregation, we summarize in this Perspective the knowledge and putative future directions of protein AMPylation research.