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FICD activity and AMPylation remodelling modulate human neurogenesis.
Nat. Commun. 11:517 (2020)
Posttranslational 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.
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12.121
2.847
18
24
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Posttranslational Modifications; Endoplasmic-reticulum; Protein; Mechanism; Proteomics; Diversity; Discovery; Reveals; Gtpases; Enzyme
Language
english
Publication Year
2020
HGF-reported in Year
2020
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Journal
Nature Communications
Quellenangaben
Volume: 11,
Issue: 1,
Article Number: 517
Publisher
Nature Publishing Group
Publishing Place
London
Reviewing status
Peer reviewed
Institute(s)
Institute of Stem Cell Research (ISF)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Stem Cell and Neuroscience
PSP Element(s)
G-552400-001
WOS ID
WOS:000543968200011
Scopus ID
85078178493
PubMed ID
31980631
Erfassungsdatum
2020-04-01