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Balta, E.A.* ; Schäffner, I.* ; Wittmann, M.T.* ; Sock, E.* ; von Zweydorf, F.* ; von Wittgenstein, J.* ; Steib, K. ; Heim, B.* ; Kremmer, E. ; Häberle, B.M.* ; Ueffing, M.* ; Lie, D.C.C.* ; Gloeckner, C.J.*

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

Sci. Rep. 8:16196 (2018)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Element-binding Protein; Adult Hippocampal Neurogenesis; Newly Generated Neurons; Dentate Granule Cells; Coffin-siris Syndrome; Camp-response; Kinase-a; Mouse Hippocampus; Stem-cell; Integration
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 8, Heft: 1, Seiten: , Artikelnummer: 16196 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
CF Monoclonal Antibodies (CF-MAB)
POF Topic(s) 30204 - Cell Programming and Repair
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Genetics and Epidemiology
Immune Response and Infection
PSP-Element(e) G-500500-001
G-501760-001
DOI 10.1038/s41598-018-34480-x
WOS ID WOS:000448950500048
Scopus ID 85055911478
PubMed ID 30385877
Erfassungsdatum 2018-11-06
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