The Hem protein mediates neuronal migration by inhibiting WAVE degradation and functions opposite of Abelson tyrosine kinase.

The Hem protein mediates neuronal migration by inhibiting WAVE degradation and functions opposite of Abelson tyrosine kinase.
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Hem 蛋白通过抑制 WAVE 降解来介导神经元迁移,其功能与 Abelson 酪氨酸激酶相反。

DOI:
10.1016/j.ydbio.2011.06.025
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发表时间:
2011
影响因子:
2.7
通讯作者:
Bhat,KrishnaMoorthi
Bhat,KrishnaMoorthi
中科院分区:
生物学3区
文献类型:
--
作者:
Zhu,Zengrong;Bhat,KrishnaMoorthi

文献摘要

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在神经系统中,神经元在不同的区域形成,然后它们迁移并占据特定的位置。我们以前已经表明,RP2/同胞,一个充分研究的神经元对果蝇腹神经索(VNC),有一个复杂的迁移路线。在这里,我们表明,Hem蛋白,通过WAVE复合物,调节迁移的GMC-1及其后代RP 2神经元。在Hem或WAVE突变体中,RP 2神经元要么异常迁移,从一个半节跨越中线到对侧半节,要么不迁移,不能发出轴突投射。我们报告,Hem通过稳定WAVE调节神经元迁移。由于Hem和WAVE通常形成复合物,因此我们的数据表明,在没有Hem的情况下,WAVE可能不再处于复合物中,变得容易降解。我们还发现,Abelson酪氨酸激酶影响RP2迁移的方式与Hem和WAVE相似,似乎是通过WAVE起作用的。然而,虽然Abl负性调节WAVE的水平,但其通过调节WAVE的活性来调节迁移。我们的研究结果还表明,在WAVE的退化过程中,Hem函数是相反的和下游的ESTA的。
In the nervous system, neurons form in different regions, then they migrate and occupy specific positions. We have previously shown that RP2/sib, a well-studied neuronal pair in the Drosophila ventral nerve cord (VNC), has a complex migration route. Here, we show that the Hem protein, via the WAVE complex, regulates migration of GMC-1 and its progeny RP2 neuron. In Hem or WAVE mutants, RP2 neuron either abnormally migrates, crossing the midline from one hemisegment to the contralateral hemisegment, or does not migrate at al and fail to send out its axon projection. We report that Hem regulates neuronal migration through stabilizing WAVE. Since Hem and WAVE normally form a complex, our data argues that in the absence of Hem, WAVE, which is presumably no longer in a complex, becomes susceptible to degradation. We also find that Abelson tyrosine kinase affects RP2 migration in a similar manner as Hem and WAVE, and appears to operate via WAVE. However, while Abl negatively regulates the levels of WAVE, it regulates migration via regulating the activity of WAVE. Our results also show that during the degradation of WAVE, Hem function is opposite to that of and downstream of Abl.