Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands.
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 Utrecht, the Netherlands; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 Utrecht, the Netherlands.
Cell Rep. 2021 Jul 13;36(2):109371. doi: 10.1016/j.celrep.2021.109371.
Axons and dendrites are long extensions of neurons that contain arrays of noncentrosomal microtubules. Calmodulin-regulated spectrin-associated proteins (CAMSAPs) bind to and stabilize free microtubule minus ends and are critical for proper neuronal development and function. Previous studies have shown that the microtubule-severing ATPase katanin interacts with CAMSAPs and limits the length of CAMSAP-decorated microtubule stretches. However, how CAMSAP and microtubule minus end dynamics are regulated in neurons is poorly understood. Here, we show that the neuron-enriched protein WDR47 interacts with CAMSAPs and is critical for axon and dendrite development. We find that WDR47 accumulates at CAMSAP2-decorated microtubules, is essential for maintaining CAMSAP2 stretches, and protects minus ends from katanin-mediated severing. We propose a model where WDR47 protects CAMSAP2 at microtubule minus ends from katanin activity to ensure proper stabilization of the neuronal microtubule network.
轴突和树突是神经元的长延伸部分，其中包含一系列非中心体微管。钙调蛋白调节的血影蛋白相关蛋白（CAMSAPs）与游离微管的负端结合并稳定它们，对于正常的神经元发育和功能至关重要。先前的研究表明，微管切割 ATP 酶katanin 与 CAMSAPs 相互作用，并限制 CAMSAP 修饰的微管延伸的长度。然而，神经元中 CAMSAP 和微管负端动力学如何被调节还知之甚少。在这里，我们表明富含神经元的蛋白 WDR47 与 CAMSAPs 相互作用，对于轴突和树突的发育至关重要。我们发现 WDR47 聚集在 CAMSAP2 修饰的微管上，对于维持 CAMSAP2 延伸是必需的，并保护负端免受 katanin 介导的切割。我们提出了一个模型，其中 WDR47 保护微管负端的 CAMSAP2 免受 katanin 的活性影响，以确保神经元微管网络的正确稳定。
