Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
Department of Cell Biology, Yale University, New Haven, CT 06520, USA.
J Cell Sci. 2019 Apr 30;132(9):jcs224311. doi: 10.1242/jcs.224311.
It has long been established that neuronal growth cone navigation depends on changes in microtubule (MT) and F-actin architecture downstream of guidance cues. However, the mechanisms by which MTs and F-actin are dually coordinated remain a fundamentally unresolved question. Here, we report that the well-characterized MT polymerase, XMAP215 (also known as CKAP5), plays an important role in mediating MT-F-actin interaction within the growth cone. We demonstrate that XMAP215 regulates MT-F-actin alignment through its N-terminal TOG 1-5 domains. Additionally, we show that XMAP215 directly binds to F-actin and co-localizes with F-actin in the growth cone periphery. We also find that XMAP215 is required for regulation of growth cone morphology and response to the guidance cue, Ephrin A5. Our findings provide the first strong evidence that XMAP215 coordinates MT and F-actin interaction We suggest a model in which XMAP215 regulates MT extension along F-actin bundles into the growth cone periphery and that these interactions may be important to control cytoskeletal dynamics downstream of guidance cues. This article has an associated First Person interview with the first author of the paper.
长期以来，人们已经确定神经元生长锥的导航依赖于导向信号下游的微管（MT）和 F-肌动蛋白结构的变化。然而，MT 和 F-肌动蛋白如何双重协调的机制仍然是一个尚未解决的基本问题。在这里，我们报告了一个特征明确的微管聚合酶，XMAP215（也称为 CKAP5），在介导生长锥内的 MT-F-肌动蛋白相互作用中起着重要作用。我们证明，XMAP215 通过其 N 端 TOG1-5 结构域调节 MT-F-肌动蛋白的排列。此外，我们还表明，XMAP215 直接与 F-肌动蛋白结合，并在生长锥的外围与 F-肌动蛋白共定位。我们还发现，XMAP215 是调节生长锥形态和对导向 cue Ephrin A5 反应所必需的。我们的研究结果提供了第一个强有力的证据，证明 XMAP215 协调 MT 和 F-肌动蛋白的相互作用。我们提出了一个模型，即 XMAP215 调节 MT 沿着 F-肌动蛋白束延伸到生长锥的外围，这些相互作用可能对控制导向 cue 下游的细胞骨架动力学很重要。本文附有该论文第一作者的第一人称采访。
