GAP-43 is key to mitotic spindle control and centrosome-based polarization in neurons
GAP-43 is key to mitotic spindle control and centrosome-based polarization in neurons
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DOI：
10.4161/cc.7.3.5235
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发表时间：
2008-02
期刊：
影响因子：
4.3
通讯作者：
Rashmi Mishra;Shailesh Kumar Gupta;K. Meiri;Megin Fong;P. Thostrup;D. Juncker;S. Mani
中科院分区：
文献类型：
--
作者：
Rashmi Mishra;Shailesh Kumar Gupta;K. Meiri;Megin Fong;P. Thostrup;D. Juncker;S. Mani
在神经元中，中心体在最终有丝分裂期间的位置标志着未来轴突的出现。然而，连接中心体位置和轴突出现的分子基础是未知的。GAP-43是一种钙调素结合IQ基序蛋白，其通过以磷酸化依赖的方式与F-肌动蛋白相互作用来调节神经元细胞骨架结构。在这里，我们表明，GAP-43与中心体，并在有丝分裂和收购的小脑颗粒神经元的神经元极性起着至关重要的作用。在缺乏GAP-43的情况下，中心体位置与突起生长脱钩，并且仅能够介导形态学极化，然而轴突隔室的分子特化不发生。这些结果表明，GAP-43需要连接中心体位置的过程中生长，以产生在小脑颗粒细胞的神经元极性。
In neurons, the position of the centrosome during final mitosis marks the point of emergence of the future axon. However, the molecular underpinnings linking centrosome position to axon emergence are unknown. GAP-43 is a calmodulin-binding IQ motif protein that regulates neuronal cytoskeletal architecture by interacting with F-actin in a phosphorylation dependent manner. Here we show that GAP-43 is associated with the centrosome and plays a critical role in mitosis and acquisition of neuronal polarity in cerebellar granule neurons. In the absence of GAP-43, the centrosome position is delinked from process outgrowth and is only capable of mediating morphological polarization, however molecular specification of the axonal compartment does not take place. These results show that GAP-43 is required to link centrosome position to process outgrowth in order to generate neuronal polarity in cerebellar granule cells.