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FICD activity and AMPylation remodelling modulate human neurogenesis

Pavel Kielkowski, Isabel Y. Buchsbaum, Volker C. Kirsch, Nina C. Bach, Micha Drukker, Silvia Cappello, Stephan A. Sieber
doi: https://doi.org/10.1101/787929
Pavel Kielkowski
Department of Chemistry, Technical University of Munich, Garching, Germany.
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Isabel Y. Buchsbaum
Max Planck Institute of Psychiatry, Munich, Germany.Graduate School of Systemic Neurosciences, Ludwig-Maximilians-University Munich, Planegg, Germany
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Volker C. Kirsch
Department of Chemistry, Technical University of Munich, Garching, Germany.
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Nina C. Bach
Department of Chemistry, Technical University of Munich, Garching, Germany.
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Micha Drukker
Helmholtz Center, Munich, Germany
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Silvia Cappello
Max Planck Institute of Psychiatry, Munich, Germany.Graduate School of Systemic Neurosciences, Ludwig-Maximilians-University Munich, Planegg, Germany
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  • For correspondence: stephan.sieber@tum.de silvia_cappello@psych.mpg.de
Stephan A. Sieber
Department of Chemistry, Technical University of Munich, Garching, Germany.
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  • For correspondence: stephan.sieber@tum.de silvia_cappello@psych.mpg.de
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Abstract

Posttranslational modification (PTM) of proteins represents an important cellular mechanism for controlling diverse functions such as signalling, localisation or protein-protein interactions1. AMPylation (also termed adenylylation) has recently been discovered as a prevalent PTM for regulating protein activity2. In human cells AMPylation has been exclusively studied with the FICD protein3–6. 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.

Footnotes

  • Update of the FICD localisation.

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Posted November 26, 2019.
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FICD activity and AMPylation remodelling modulate human neurogenesis
Pavel Kielkowski, Isabel Y. Buchsbaum, Volker C. Kirsch, Nina C. Bach, Micha Drukker, Silvia Cappello, Stephan A. Sieber
bioRxiv 787929; doi: https://doi.org/10.1101/787929
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FICD activity and AMPylation remodelling modulate human neurogenesis
Pavel Kielkowski, Isabel Y. Buchsbaum, Volker C. Kirsch, Nina C. Bach, Micha Drukker, Silvia Cappello, Stephan A. Sieber
bioRxiv 787929; doi: https://doi.org/10.1101/787929

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