Pavel Kielkowski, Isabel Y Buchsbaum, Volker C Kirsch, Nina C Bach, Micha Drukker, Silvia Cappello, Stephan A Sieber
Nature communications 2020 Jan 24Posttranslational modification (PTM) of proteins represents an important cellular mechanism for controlling diverse functions such as signalling, localisation or protein-protein interactions. AMPylation (also termed adenylylation) has recently been discovered as a prevalent PTM for regulating protein activity. In human cells AMPylation has been exclusively studied with the FICD protein. Here we investigate the role of AMPylation in human neurogenesis by introducing a cell-permeable propargyl adenosine pronucleotide probe to infiltrate cellular AMPylation pathways and report distinct modifications in intact cancer cell lines, human-derived stem cells, neural progenitor cells (NPCs), neurons and cerebral organoids (COs) via LC-MS/MS as well as imaging methods. A total of 162 AMP modified proteins were identified. FICD-dependent AMPylation remodelling accelerates differentiation of neural progenitor cells into mature neurons in COs, demonstrating a so far unknown trigger of human neurogenesis.
Pavel Kielkowski, Isabel Y Buchsbaum, Volker C Kirsch, Nina C Bach, Micha Drukker, Silvia Cappello, Stephan A Sieber. FICD activity and AMPylation remodelling modulate human neurogenesis. Nature communications. 2020 Jan 24;11(1):517
PMID: 31980631
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