Commissureless regulation of axon outgrowth across the midline is independent of Rab function.

Commissureless regulation of axon outgrowth across the midline is independent of Rab function.
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DOI:
10.1371/journal.pone.0064427
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Tear G
Tear G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
van den Brink DM;Banerji O;Tear G

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神经系统的功能要求神经回路中的神经元精确地连接在一起。这些连接在轴突引导的过程中形成,每个神经元延伸轴突,通过复杂的环境迁移,通常是很长的距离,以到达其突触目标。这个任务可以通过利用中间目标将路线划分为更小的部分来简化。这就要求轴突在朝向和远离中间目标迁移时适应它们的行为。在中枢神经系统中,中线充当连合轴突的中间目标。在果蝇中,连合轴突通过调节其细胞表面上的Roundabout受体的水平,从吸引向远离中线的延伸切换。这是通过在到达中线之前将Roundabout引导到索马中的细胞内隔室来实现的。一旦穿过中线,Roundabout就可以到达表面,并作为中线细胞分泌的排斥性配体Slit的受体。在这里,我们研究了可能促进连合神经元索马内的无连合和Roundabout的细胞内靶向的候选细胞内机制。使用修改形式的Commissueless或Rabs,我们表明,无论是泛素化,也没有Rab活性是必要的Commissueless的细胞内靶向。此外,我们揭示了果蝇中枢神经系统内许多神经元群体的轴突生长也独立于Rab活性。
Nervous system function requires that neurons within neural circuits are connected together precisely. These connections form during the process of axon guidance whereby each neuron extends an axon that migrates, often large distances, through a complex environment to reach its synaptic target. This task can be simplified by utilising intermediate targets to divide the route into smaller sections. This requires that axons adapt their behaviour as they migrate towards and away from intermediate targets. In the central nervous system the midline acts as an intermediate target for commissural axons. In Drosophila commissural axons switch from attraction towards to extension away from the midline by regulating the levels of the Roundabout receptor on their cell surface. This is achieved by Commissureless which directs Roundabout to an intracellular compartment in the soma prior to reaching the midline. Once across the midline Roundabout is allowed to reach the surface and acts as a receptor for the repellent ligand Slit that is secreted by cells at the midline. Here we investigated candidate intracellular mechanisms that may facilitate the intracellular targeting of Commissureless and Roundabout within the soma of commissural neurons. Using modified forms of Commissureless or Rabs we show that neither ubiquitination nor Rab activity are necessary for the intracellular targeting of Commissureless. In addition we reveal that axon outgrowth of many populations of neurons within the Drosophila central nervous system is also independent of Rab activity.
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