PtdIns (3,4,5) P3 Recruitment of Myo10 Is Essential for Axon Development
PtdIns (3,4,5) P3 Recruitment of Myo10 Is Essential for Axon Development
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PtdIns (3,4,5) P3 Myo10 的招募对于轴突发育至关重要
DOI：
10.1371/journal.pone.0036988
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发表时间：
2012-05
期刊：
影响因子：
3.7
通讯作者：
Xiaojuan Zhu
中科院分区：
文献类型：
--
作者：
Muhammad Abid Sheikh,;Jianhua Zhang;Xingzhi Wang;Xiaojuan Zhu
肌球蛋白X(myosin X，Myo10)是一种肌球蛋白X(myosin X，Myo10)，具有Pleckstrin Homology(PH)结构域，是一种参与丝状基团起始和延伸的马达蛋白。然而，它的潜在作用还没有被完全了解，特别是在神经元发育中。本研究利用抗Myo10抗体的免疫荧光结合抗Tuj1抗体作为特异性标记物，在原代培养的海马神经元中发现了Myo10在轴突尖端的优势聚集。Myo10基因转录下调后轴突生长受损，Tau-1阳性表型丢失。有趣的是，细胞松弛素D对肌动蛋白聚合的抑制挽救了轴突生长的缺陷。此外，用增强型绿色荧光蛋白(EGFP)标记的Myo10突变体异位表达Myo10以一种运动非依赖性的方式诱导了多个轴突。机制研究表明，Myo10通过其PH结构域募集到磷脂酰肌醇(3，4，5)-三磷酸(PtdIns(3，4，5)P3)是轴突形成所必需的。此外，体内研究证实，在发育中的新皮质中，在径向神经元迁移过程中，Myo10是神经元形态转变所必需的。
Myosin X (Myo10) with pleckstrin homology (PH) domains is a motor protein acting in filopodium initiation and extension. However, its potential role has not been fully understood, especially in neuronal development. In the present study the preferential accumulation of Myo10 in axon tips has been revealed in primary culture of hippocampal neurons with the aid of immunofluorescence from anti-Myo10 antibody in combination with anti-Tuj1 antibody as specific marker. Knocking down Myo10 gene transcription impaired outgrowth of axon with loss of Tau-1-positive phenotype. Interestingly, inhibition of actin polymerization by cytochalasin D rescued the defect of axon outgrowth. Furthermore, ectopic expression of Myo10 with enhanced green fluorescence protein (EGFP) labeled Myo10 mutants induced multiple axon-like neurites in a motor-independent way. Mechanism studies demonstrated that the recruitment of Myo10 through its PH domain to phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5) P3) was essential for axon formation. In addition, in vivo studies confirmed that Myo10 was required for neuronal morphological transition during radial neuronal migration in the developmental neocortex.
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DOI：
10.1083/jcb.200804062
发表时间：
2008-07-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Woolner S;O'Brien LL;Wiese C;Bement WM
通讯作者：
Bement WM
影响因子：
3
作者：
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影响因子：
3
作者：
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通讯作者：
M. Stiess;F. Bradke
影响因子：
25
作者：
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通讯作者：
Püschel, AW
DOI：
10.1016/j.bbrc.2004.04.167
发表时间：
2004-06-18
影响因子：
3.1
作者：
Tokuo, H;Ikebe, M
通讯作者：
Ikebe, M