PT  - JOURNAL ARTICLE
AU  - Pavel Kielkowski
AU  - Isabel Y. Buchsbaum
AU  - Volker C. Kirsch
AU  - Nina C. Bach
AU  - Micha Drukker
AU  - Silvia Cappello
AU  - Stephan A. Sieber
TI  - FICD activity and AMPylation remodelling modulate human neurogenesis
AID  - 10.1101/787929
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 787929
4099  - http://biorxiv.org/content/early/2019/10/01/787929.short
4100  - http://biorxiv.org/content/early/2019/10/01/787929.full
AB  - 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.