β-Spectrin functions independently of Ankyrin to regulate the establishment and maintenance of axon connections in the Drosophila embryonic CNS
β-Spectrin functions independently of Ankyrin to regulate the establishment and maintenance of axon connections in the Drosophila embryonic CNS
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DOI：
10.1242/dev.02653
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发表时间：
2007-01-15
期刊：
影响因子：
4.6
通讯作者：
Bashaw, Greg J.
中科院分区：
文献类型：
--
作者：
Garbe, David S.;Das, Amlan;Bashaw, Greg J.
α-和β-血影蛋白是连接肌动蛋白丝和完整质膜蛋白的亚膜细胞骨架网络的主要组成部分。除了在红细胞中的结构作用外，血影蛋白网络还被认为在蛋白质靶向和膜结构域形成过程中在非红细胞中发挥作用。在这里，我们证明了果蝇胚胎 CNS 神经元中需要 β-Spectrin 来正确引导中线轴突。在β-血影蛋白突变体中，许多轴突不适当地穿过中枢神经系统中线，表明β-血影蛋白在中线排斥中发挥作用。令人惊讶的是，准确的指导决策不需要 β-血影蛋白的锚蛋白结合域和普莱克斯特林同源 (PH) 域。 β-血影蛋白的正常亚细胞定位和/或维持依赖于β-血影蛋白，而β-血影蛋白突变体表现出β-血影蛋白向轴突支架的重新分布。 β-血影蛋白突变体与中线排斥狭缝及其神经元受体环形交叉口（robo）表现出特定的剂量依赖性遗传相互作用，但与其他引导分子没有相互作用。结果表明，β-血影蛋白通过调节 Slit-Robo 通路成分来促进中线排斥。我们认为，血影蛋白网络在建立和/或维护含有引导分子的专门膜域中独立于锚蛋白发挥作用，以确保中线轴突排斥的保真度。
alpha- and beta-Spectrin are major components of a submembrane cytoskeletal network connecting actin filaments to integral plasma membrane proteins. Besides its structural role in red blood cells, the Spectrin network is thought to function in non-erythroid cells during protein targeting and membrane domain formation. Here, we demonstrate that beta-Spectrin is required in neurons for proper midline axon guidance in the Drosophila embryonic CNS. In beta-spectrin mutants many axons inappropriately cross the CNS midline, suggesting a role for beta-Spectrin in midline repulsion. Surprisingly, neither the Ankyrin-binding nor the pleckstrin homology ( PH) domains of beta- Spectrin are required for accurate guidance decisions. beta-Spectrin is dependent upon beta-Spectrin for its normal subcellular localization and/or maintenance, whereas beta-spectrin mutants exhibit a redistribution of beta-Spectrin to the axon scaffold. beta-spectrin mutants show specific dose- dependent genetic interactions with the midline repellent slit and its neuronal receptor roundabout (robo), but not with other guidance molecules. The results suggest that beta-Spectrin contributes to midline repulsion through the regulation of Slit-Robo pathway components. We propose that the Spectrin network is playing a role independently of Ankyrin in the establishment and/or maintenance of specialized membrane domains containing guidance molecules that ensure the fidelity of axon repulsion at the midline.