Axon branching requires interactions between dynamic microtubules and actin filaments
Axon branching requires interactions between dynamic microtubules and actin filaments
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DOI：
10.1523/jneurosci.21-24-09757.2001
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发表时间：
2001-12-15
影响因子：
5.3
通讯作者：
Kalil, K
中科院分区：
文献类型：
--
作者：
Dent, EW;Kalil, K
皮质神经元通过侧支轴突分支来支配它们的许多靶点，这需要细胞骨架的局部重组。我们共注射皮质神经元与荧光标记的微管蛋白和鬼笔环肽，并使用荧光时间推移成像分析微管和肌动蛋白丝（F-肌动蛋白）在皮质生长锥和轴突进行分支之间的相互作用。在生长锥和轴突分支点，成环或成束微管的张开伴随着F-肌动蛋白的局灶性积聚。动态微管与F-肌动蛋白共定位在生长锥的过渡区和轴突分支点。相反，F-肌动蛋白被排除在生长锥和轴突轴的中心区域，其中包含稳定的微管。动态微管和动态肌动蛋白丝之间的相互作用涉及它们的协调聚合和解聚。应用减弱微管或F-肌动蛋白动力学的药物也抑制其他细胞骨架元件的聚合。重要的是，微管或F-肌动蛋白动力学的抑制防止轴突分支，但不是轴突伸长。然而，这些治疗确实会导致无方向的轴突生长。这些结果表明，动态微管和肌动蛋白丝之间的相互作用所需的轴突分支和定向轴突生长。
Cortical neurons innervate many of their targets by collateral axon branching, which requires local reorganization of the cytoskeleton. We coinjected cortical neurons with fluorescently labeled tubulin and phalloidin and used fluorescence time-lapse imaging to analyze interactions between microtubules and actin filaments (F-actin) in cortical growth cones and axons undergoing branching. In growth cones and at axon branch points, splaying of looped or bundled microtubules is accompanied by focal accumulation of F-actin. Dynamic microtubules colocalize with F-actin in transition regions of growth cones and at axon branch points. In contrast, F-actin is excluded from the central region of the growth cone and the axon shaft, which contains stable microtubules. Interactions between dynamic microtubules and dynamic actin filaments involve their coordinated polymerization and depolymerization. Application of drugs that attenuate either microtubule or F-actin dynamics also inhibits polymerization of the other cytoskeletal element. Importantly, inhibition of microtubule or F-actin dynamics prevents axon branching but not axon elongation. However, these treatments do cause undirected axon outgrowth. These results suggest that interactions between dynamic microtubules and actin filaments are required for axon branching and directed axon outgrowth.