Balta Elli-Anna, Wittmann Marie-Theres, Jung Matthias, Sock Elisabeth, Haeberle Benjamin Martin, Heim Birgit, von Zweydorf Felix, Heppt Jana, von Wittgenstein Julia, Gloeckner Christian Johannes, Lie Dieter Chichung
Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Center for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany.
Front Mol Neurosci. 2018 Jun 19;11:211. doi: 10.3389/fnmol.2018.00211. eCollection 2018.
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.
SOX11是胚胎和成年神经发生调节中的关键转录因子（TF），其突变最近与人类智力残疾综合征有关。SOX11在神经发生过程中的短暂活性对于确保神经发生程序的精确执行至关重要。在这里，我们报告SOX11在神经发生过程中表现出不同的亚细胞定位。对胚胎小鼠脑裂解物的蛋白质免疫印迹分析表明，SOX11通过磷酸化进行翻译后修饰。使用质谱法，我们在SOX11蛋白中发现了10个可能被磷酸化的丝氨酸残基。对磷酸化突变体SOX11的系统分析导致鉴定出S30残基，其磷酸化促进SOX11的核定位而非细胞质定位。这些发现共同揭示了磷酸化是智力残疾基因Sox11调节的新层面。
