FICD activity and AMPylation remodelling modulate human neurogenesis

Autor: Nina C. Bach, Isabel Y. Buchsbaum, Volker C. Kirsch, Pavel Kielkowski, Silvia Cappello, Stephan A. Sieber, Micha Drukker
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Proteomics
Adenosine
Cellular differentiation
General Physics and Astronomy
Cathepsin B
Cellular mechanism
0302 clinical medicine
Neural Stem Cells
lcsh:Science
Neurons
0303 health sciences
Multidisciplinary
Chemistry
Neurogenesis
Cell Differentiation
Nucleotidyltransferases
Neural stem cell
ddc
Cell biology
Organoids
Signalling
Stem cell
medicine.drug
Science
Down-Regulation
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
Organoid
medicine
Humans
Amino Acid Sequence
Adenylylation
030304 developmental biology
Membrane Proteins
General Chemistry
Adenosine Monophosphate
030104 developmental biology
Cell culture
Neuronal development
lcsh:Q
Protein Processing
Post-Translational
030217 neurology & neurosurgery
Post-translational modifications
Zdroj: Nature Communications
Nat. Commun. 11:517 (2020)
Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020)
ISSN: 2041-1723
Popis: 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.
Protein AMPylation is a post-translational modification whose implications in cellular physiology are not fully understood. Here the authors develop a cell-permeable AMPylation probe and use it to identify new AMP modified proteins and investigate the role of FICD in neuronal differentiation using cerebral organoids.
Databáze: OpenAIRE
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