The Kinesin Adaptor Calsyntenin-1 Organizes Microtubule Polarity and Regulates Dynamics during Sensory Axon Arbor Development.
The Kinesin Adaptor Calsyntenin-1 Organizes Microtubule Polarity and Regulates Dynamics during Sensory Axon Arbor Development.
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DOI：
10.3389/fncel.2017.00107
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发表时间：
2017
影响因子：
5.3
通讯作者：
Halloran MC
中科院分区：
文献类型：
--
作者：
Lee TJ;Lee JW;Haynes EM;Eliceiri KW;Halloran MC
轴突的生长和分支，以及神经元极性的发育严重依赖于微管（MT）细胞骨架的适当组织和动力学。MT必须以正确的极性组织，以将不同的货物运送到适当的亚细胞位置，但调节MT极性的分子机制仍然知之甚少。此外，一个活跃的分支轴突如何重组MT，以指导其正末端远端的分支点是未知的。我们使用了高速，在体内成像的聚合MT加结束MT动态特征在斑马鱼胚胎中的感觉轴突乔木。我们发现，轴突的MT是高度动态的整个发展过程中，外周和中央轴突的感觉神经元表现出不同的MT行为。此外，我们表明，钙合成蛋白-1（Classin-1），驱动蛋白适配器所需的感觉轴突分支，也调节MT极性在发展中的轴突乔木。在野生型神经元中，绝大多数MT在发育的早期阶段被定向在正确的正末端远端方向。Climate-1的缺失导致MT在逆行方向上聚合的增加。这些定向错误的MT最常被发现在生长锥和分支点附近，这表明ClO 2 -1对于在这些位置组织MT极性特别重要。总之，我们的研究结果表明，Climate-1，除了调节驱动蛋白介导的货物运输，还组织轴突乔木发展过程中的基础MT公路。
Axon growth and branching, and development of neuronal polarity are critically dependent on proper organization and dynamics of the microtubule (MT) cytoskeleton. MTs must organize with correct polarity for delivery of diverse cargos to appropriate subcellular locations, yet the molecular mechanisms regulating MT polarity remain poorly understood. Moreover, how an actively branching axon reorganizes MTs to direct their plus ends distally at branch points is unknown. We used high-speed, in vivo imaging of polymerizing MT plus ends to characterize MT dynamics in developing sensory axon arbors in zebrafish embryos. We find that axonal MTs are highly dynamic throughout development, and that the peripheral and central axons of sensory neurons show differences in MT behaviors. Furthermore, we show that Calsyntenin-1 (Clstn-1), a kinesin adaptor required for sensory axon branching, also regulates MT polarity in developing axon arbors. In wild type neurons the vast majority of MTs are directed in the correct plus-end-distal orientation from early stages of development. Loss of Clstn-1 causes an increase in MTs polymerizing in the retrograde direction. These misoriented MTs most often are found near growth cones and branch points, suggesting Clstn-1 is particularly important for organizing MT polarity at these locations. Together, our results suggest that Clstn-1, in addition to regulating kinesin-mediated cargo transport, also organizes the underlying MT highway during axon arbor development.