Mouse ACF7 and Drosophila Short stop modulate filopodia formation and microtubule organisation during neuronal growth
Mouse ACF7 and Drosophila Short stop modulate filopodia formation and microtubule organisation during neuronal growth
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DOI：
10.1242/jcs.046268
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发表时间：
2009-07-15
影响因子：
4
通讯作者：
Prokop, Andreas
中科院分区：
文献类型：
--
作者：
Sanchez-Soriano, Natalia;Travis, Mark;Prokop, Andreas
Spectraplakins是一种大的肌动蛋白-微管连接分子，参与各种过程，包括原肠胚形成、伤口愈合、皮肤起泡和神经元变性。哺乳动物spectraplakin ACF 7的表达数据和果蝇spectraplakin Short stop（Shot）的遗传分析表明在神经发生过程中起重要作用。使用三个平行的神经元培养系统，我们证明，像射击，ACF 7是必不可少的轴突延伸和描述，第一次，他们的亚细胞功能轴突生长过程中。首先，ACF 7和Shot都调节神经元微管的组织，这一作用依赖于F-肌动蛋白和微管结合结构域。微管组织中的这种作用可能是Shot和ACF 7在生长锥推进中的作用的关键机制。其次，我们发现ACF 7和Shot通过其控制丝状伪足形成的能力来调节肌动蛋白细胞骨架的新作用。这种功能在F-肌动蛋白的调节需要EF-手图案和相互作用的翻译调节Krasavietz/eIF 5C，表明潜在的机制是完全不同的，从那些用来控制微管。我们的数据为Shot和ACF 7在神经系统发育中的作用的第一个机械解释提供了基础，并证明了它们在轴突生长过程中协调肌动蛋白和微管网络组织的能力。
Spectraplakins are large actin-microtubule linker molecules implicated in various processes, including gastrulation, wound healing, skin blistering and neuronal degeneration. Expression data for the mammalian spectraplakin ACF7 and genetic analyses of the Drosophila spectraplakin Short stop ( Shot) suggest an important role during neurogenesis. Using three parallel neuronal culture systems we demonstrate that, like Shot, ACF7 is essential for axon extension and describe, for the first time, their subcellular functions during axonal growth. Firstly, both ACF7 and Shot regulate the organisation of neuronal microtubules, a role dependent on both the F-actin-and microtubule-binding domains. This role in microtubule organisation is probably the key mechanism underlying the roles of Shot and ACF7 in growth cone advance. Secondly, we found a novel role for ACF7 and Shot in regulating the actin cytoskeleton through their ability to control the formation of filopodia. This function in F-actin regulation requires EF-hand motifs and interaction with the translational regulator Krasavietz/eIF5C, indicating that the underlying mechanisms are completely different from those used to control microtubules. Our data provide the basis for the first mechanistic explanation for the role of Shot and ACF7 in the developing nervous system and demonstrate their ability to coordinate the organisation of both actin and microtubule networks during axonal growth.