Phosphorylation Modulates the Subcellular Localization of SOX11.

Elli-Anna Balta,Birgit Heim,Benjamin Martin Haeberle,Jana Heppt,Matthias Jung,Dieter Chichung Lie,Marie-Theres Wittmann,Julia Von Wittgenstein,Felix Von Zweydorf,Elisabeth Sock,Christian Johannes Gloeckner

doi:10.3389/fnmol.2018.00211

Abstract

SOX11 is a key Transcription Factor (TF) in the regulation of embryonic and adult neurogenesis, whose mutation has recently been linked to an intellectual disability syndrome in humans. SOX11’s transient activity during neurogenesis is critical to ensure the precise execution of the neurogenic program. Here, we report that SOX11 displays differential subcellular localizations during the course of neurogenesis. Western-Blot analysis of embryonic mouse brain lysates indicated that SOX11 is post-translationally modified by phosphorylation. Using Mass Spectrometry, we found 10 serine residues in the SOX11 protein that are putatively phosphorylated. Systematic analysis of phospho-mutant SOX11 resulted in the identification of the S30 residue, whose phosphorylation promotes nuclear over cytoplasmic localization of SOX11. Collectively, these findings uncover phosphorylation as a novel layer of regulation of the intellectual disability gene Sox11.

Highlights

SOX11 (SRY-related HMG-box 11) is a member of the SoxC Transcription Factor (TF) family
SOX11 is found in both nucleus and cytoplasm in cells of the subgranular zone of the dentate gyrus (DG), the subventricular zone (SVZ) of the lateral ventricles, the rostral migratory stream (RMS) and the olfactory bulb (OB; Figure 2)
These results demonstrate that SOX11 can localize to the nucleus and to the cytoplasm during embryonic and adult neurogenesis

Summary

Introduction

SOX11 (SRY-related HMG-box 11) is a member of the SoxC Transcription Factor (TF) family. The SoxC family, which in addition to SOX11 comprises SOX4 and SOX12, potently regulates the development of the mammalian nervous system (Wegner, 2011; Kavyanifar et al, 2018). Sox expression is strongly associated with neurogenic activity and is with regard to the central nervous system (CNS) largely confined to the embryonic (Uwanogho et al, 1995; Hargrave et al, 1997; Rimini et al, 1999; Sock et al, 2004) and adult germinal zones (Mu et al, 2012; Wang et al, 2013). Recent findings indicate that the expression of SOX11 itself and its transient activity is critical to ensure the precise execution of the neurogenic program (Hoshiba et al, 2016). Sox ablation in developing cortical neurons results in premature development of an elaborate dendrite compartment and Phosphorylation-Dependent Localization of Sox migration deficits; whereas, Sox overexpression does not affect neuronal migration but severely impairs dendritic development (Hoshiba et al, 2016)

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Conclusion