Synaptojanin-1 plays a key role in astrogliogenesis: possible relevance for Down's syndrome
Synaptojanin-1 plays a key role in astrogliogenesis: possible relevance for Down's syndrome
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DOI：
10.1038/cdd.2009.24
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发表时间：
2009-06-01
影响因子：
12.4
通讯作者：
Schubert, D. R.
中科院分区：
文献类型：
--
作者：
Herrera, F.;Chen, Q.;Schubert, D. R.
随着人们更好地了解神经胶质细胞与大脑发育和病理学的相关性，人们对神经胶质细胞生成越来越感兴趣。然而，人们对这个过程知之甚少。使用多维蛋白质识别技术（MudPIT）来鉴定经细胞因子或视黄酸处理的大鼠神经前体细胞中磷蛋白水平的变化，结果表明磷脂酰肌醇-4,5-二磷酸3-激酶（PI3K p110 α）催化亚基的磷酸化和肌醇磷酸酶 synaptojanin-1 的去磷酸化对于胶质生成刺激是常见的。尽管发现 PI3K 参与神经和星形胶质细胞生成，但 synaptojanin-1 特别参与神经前体细胞的星形胶质细胞生成。通过对 synaptojanin-1 敲除小鼠大脑中神经元和胶质细胞特异性标记物的分析，进一步证实了 synaptojanin-1 在星形胶质细胞生成中的作用。其他实验表明 synaptojanin-1 的 Sac1 样磷酸酶结构域是观察到的星形胶质细胞生成效应的原因。我们的结果强烈表明磷脂酰肌醇代谢在星形胶质细胞生成中起着关键作用。讨论了我们的研究结果与唐氏综合症病理学的相关性。细胞死亡与分化 (2009) 16, 910-920; doi：10.1038/cdd.2009.24； 2009 年 3 月 13 日在线发布
There is increasing interest in gliogenesis as the relevance of glia to both brain development and pathology becomes better understood. However, little is known about this process. The use of multidimensional protein identification technology (MudPIT) to identify changes in phosphoprotein levels in rat neural precursor cells treated with cytokines or retinoic acid showed that phosphorylation of the catalytic subunit of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K p110 alpha) and dephosphorylation of the inositol phosphatase synaptojanin-1 were common to the gliogenic stimuli. Although PI3K was found to be involved in both neuro-and astrogliogenesis, synaptojanin-1 was specifically involved in astrogliogenesis of neural precursor cells. The role of synaptojanin-1 in astrogliogenesis was further confirmed by analysis of neuron-and glia-specific markers in synaptojanin-1 knockout mouse brain. Additional experiments showed that the Sac1-like phosphatase domain of synaptojanin-1 is responsible for the observed astrogliogenic effect. Our results strongly indicate that phosphatidylinositol metabolism plays a key role in astrogliogenesis. The relevance of our findings for Down's syndrome pathology is discussed. Cell Death and Differentiation (2009) 16, 910-920; doi: 10.1038/cdd.2009.24; published online 13 March 2009