WDR47 protects neuronal microtubule minus ends from katanin-mediated severing
WDR47 protects neuronal microtubule minus ends from katanin-mediated severing
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DOI：
10.1016/j.celrep.2021.109371
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发表时间：
2021-07-13
期刊：
影响因子：
8.8
通讯作者：
Hoogenraad, Casper C.
中科院分区：
文献类型：
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作者：
Buijs, Robin R.;Hummel, Jessica J. A.;Hoogenraad, Casper C.
轴突和树突是神经元的长延伸，包含非中心体微管阵列。钙调素调节的光谱相关蛋白（CAMSAPs）结合并稳定游离微管负端，对神经元的正常发育和功能至关重要。先前的研究表明，切断微管的atp酶katanin与camsap相互作用，并限制camsap修饰的微管延伸的长度。然而，CAMSAP和微管负端动力学在神经元中是如何调节的，人们知之甚少。在这里，我们发现神经元富集蛋白WDR47与CAMSAPs相互作用，对轴突和树突的发育至关重要。我们发现WDR47在CAMSAP2修饰的微管中积累，对维持CAMSAP2的延伸至关重要，并保护负端免受katanin介导的切断。我们提出了一个模型，其中WDR47保护微管负端的CAMSAP2免受katanin活性的影响，以确保神经元微管网络的适当稳定。
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.