Phosphorylation of the neurogenic transcription factor SOX11 on serine 133 modulates neuronal morphogenesis

Autor: Kathrin Steib, Birgit Heim, Felix von Zweydorf, Elli-Anna Balta, Marius Ueffing, Benjamin M. Häberle, Iris Schäffner, Elisabeth Sock, Julia von Wittgenstein, Elisabeth Kremmer, Dieter Chichung Lie, Marie-Theres Wittmann, Christian Johannes Gloeckner
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
growth & development [Cerebellar Nuclei]
Neurogenesis
Regulator
Morphogenesis
lcsh:Medicine
metabolism [Hippocampus]
genetics [SOXC Transcription Factors]
Hippocampal formation
Hippocampus
Article
Mass Spectrometry
SOXC Transcription Factors
Serine
genetics [Dendrites]
Mice
03 medical and health sciences
Mediator
Animals
metabolism [Dendrites]
Phosphorylation
genetics [Phosphorylation]
Protein kinase A
lcsh:Science
Transcription factor
Neurons
Multidisciplinary
Chemistry
genetics [Cyclic AMP-Dependent Protein Kinases]
chemistry [Cyclic AMP-Dependent Protein Kinases]
lcsh:R
genetics [Serine]
Dendrites
Cyclic AMP-Dependent Protein Kinases
growth & development [Hippocampus]
Cell biology
genetics [Morphogenesis]
Sox11 protein
mouse
030104 developmental biology
Cerebellar Nuclei
genetics [Neurogenesis]
metabolism [Neurons]
lcsh:Q
ddc:600
metabolism [Cerebellar Nuclei]
Zdroj: Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
Scientific Reports
Scientific reports 8(1), 16196 (2018). doi:10.1038/s41598-018-34480-x
ISSN: 2045-2322
Popis: The intellectual disability gene, Sox11, encodes for a critical neurodevelopmental transcription factor with functions in precursor survival, neuronal fate determination, migration and morphogenesis. The mechanisms regulating SOX11’s activity remain largely unknown. Mass spectrometric analysis uncovered that SOX11 can be post-translationally modified by phosphorylation. Here, we report that phosphorylatable serines surrounding the high-mobility group box modulate SOX11’s transcriptional activity. Through Mass Spectrometry (MS), co-immunoprecipitation assays and in vitro phosphorylation assays followed by MS we verified that protein kinase A (PKA) interacts with SOX11 and phosphorylates it on S133. In vivo replacement of SoxC factors in developing adult-generated hippocampal neurons with SOX11 S133 phospho-mutants indicated that phosphorylation on S133 modulates dendrite development of adult-born dentate granule neurons, while reporter assays suggested that S133 phosphorylation fine-tunes the activation of select target genes. These data provide novel insight into the control of the critical neurodevelopmental regulator SOX11 and imply SOX11 as a mediator of PKA-regulated neuronal development.
Databáze: OpenAIRE
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