Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, United States.
Department of Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, United States.
Elife. 2018 Aug 22;7:e36374. doi: 10.7554/eLife.36374.
Neuronal cell morphogenesis depends on proper regulation of microtubule-based transport, but the underlying mechanisms are not well understood. Here, we report our study of MAP7, a unique microtubule-associated protein that interacts with both microtubules and the motor protein kinesin-1. Structure-function analysis in rat embryonic sensory neurons shows that the kinesin-1 interacting domain in MAP7 is required for axon and branch growth but not for branch formation. Also, two unique microtubule binding sites are found in MAP7 that have distinct dissociation kinetics and are both required for branch formation. Furthermore, MAP7 recruits kinesin-1 dynamically to microtubules, leading to alterations in organelle transport behaviors, particularly pause/speed switching. As MAP7 is localized to branch sites, our results suggest a novel mechanism mediated by the dual interactions of MAP7 with microtubules and kinesin-1 in the precise control of microtubule-based transport during axon morphogenesis.
神经元细胞形态发生依赖于微管基运输的正确调节，但潜在机制尚不清楚。在这里，我们报告了我们对 MAP7 的研究，MAP7 是一种独特的微管相关蛋白，与微管和驱动蛋白 kinesin-1 相互作用。在大鼠胚胎感觉神经元中的结构-功能分析表明，MAP7 中的 kinesin-1 相互作用域对于轴突和分支生长是必需的，但对于分支形成不是必需的。此外，在 MAP7 中发现了两个独特的微管结合位点，它们具有不同的解离动力学，并且对于分支形成都是必需的。此外，MAP7 动态地将 kinesin-1 募集到微管上，导致细胞器运输行为的改变，特别是暂停/速度切换。由于 MAP7 定位于分支位点，我们的结果表明，在轴突形态发生过程中，通过 MAP7 与微管和驱动蛋白 kinesin-1 的双重相互作用，介导了一种精确控制微管基运输的新机制。
