Wnt regulates axon behavior through changes in microtubule growth directionality: a new role for adenomatous polyposis coli.
Wnt regulates axon behavior through changes in microtubule growth directionality: a new role for adenomatous polyposis coli.
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DOI：
10.1523/jneurosci.2320-08.2008
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发表时间：
2008-08-20
期刊：
影响因子：
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通讯作者：
Salinas PC
中科院分区：
文献类型：
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作者：
Purro SA;Ciani L;Hoyos-Flight M;Stamatakou E;Siomou E;Salinas PC
轴突引导和目标衍生信号通过不明确的机制调节细胞骨架来控制轴突行为。特别是，这些信号分子如何调节微管的生长和方向性尚不清楚。在这里，我们研究了wnt对生长锥重塑的影响，这是一个先于突触形成的过程。延时记录显示Wnt3a快速抑制生长锥易位，同时诱导生长锥增大。轴突行为的这些变化与微管组织的变化有关。EB3-GFP（绿色荧光蛋白）标记的微管正端延时成像显示，Wnt3a调节微管的方向性，导致微管环化、生长锥暂停和重构。对Dvl1突变神经元的分析表明，Dvl1是wnt介导的微管重组和轴突重塑所必需的。Wnt信号通过意想不到地诱导微管正端APC丢失直接影响微管细胞骨架。一致地，APC shRNA敲低模仿Wnt3a功能。总之，我们的研究结果将APC定义为调控微管生长方向的关键Wnt信号靶点。
Axon guidance and target-derived signals control axonal behavior by regulating the cytoskeleton through poorly defined mechanisms. In particular, how these signalling molecules regulate the growth and directionality of microtubules is not well understood. Here we examine the effect of Wnts on growth cone remodelling, a process that precedes synapse formation. Time-lapse recordings reveal that Wnt3a rapidly inhibits growth cone translocation while inducing growth cone enlargement. These changes in axonal behavior are associated with changes in the organization of microtubules. Time-lapse imaging of EB3-GFP (green fluorescent protein) labeled microtubule plus-ends demonstrates that Wnt3a regulates microtubule directionality, resulting in microtubule looping, growth cone pausing and remodelling. Analyzes of Dvl1 mutant neurons demonstrate that Dvl1 is required for Wnt-mediated microtubule reorganization and axon remodelling. Wnt signalling directly affects the microtubule cytoskeleton by unexpectedly inducing APC loss from microtubule plus-ends. Consistently, shRNA knockdown of APC mimics Wnt3a function. Together our findings define APC as a key Wnt signalling target in the regulation of microtubule growth direction.