Spastin Interacts with CRMP5 to Promote Neurite Outgrowth by Controlling the Microtubule Dynamics
Spastin Interacts with CRMP5 to Promote Neurite Outgrowth by Controlling the Microtubule Dynamics
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Spastin 与 CRMP5 相互作用，通过控制微管动力学促进神经突生长
DOI：
10.1002/dneu.22640
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发表时间：
2018-12-01
影响因子：
3
通讯作者：
Guo, Guoqing
中科院分区：
文献类型：
--
作者：
Ji, Zhisheng;Zhang, Guowei;Guo, Guoqing
改变微管动力学足以改变轴突和树突的规格和发育。Spastin通过将微管切割成小段参与神经突的生长和再生，而坍缩反应介质蛋白5 （CRMP5）通过促进微管聚合提供结构支持并作为货物运输的轨道。然而，spastin和CRMP5如何通过控制微管动力学来协同调节神经突生长还有待阐明。在我们目前的研究中，spastin在体外和体内与CRMP5相互作用。spastin和CRMP5相互作用的结合域是spastin的N端片段（残基270-328）和CRMP5的C端片段（残基472-564）。Spastin及其截断突变体，包括微管结合结构域（MTBD）和与多种细胞活性相关的atp酶（AAA）结构域，是切断微管所必需的。此外，我们证明了CRMP5的微管聚合干扰了spastin的微管切断功能。抑制spastin或CRMP5均可抑制海马神经元的神经突生长。然而，共转染spastin和CRMP5促进了包括树突和轴突在内的神经突的生长。综上所述，我们的数据支持spastin与CRMP5的相互作用通过控制微管动力学来促进神经突生长的模型。
Changing the microtubule dynamics is sufficient to alter the axon and dendrite specification and development. Spastin participates in the growth and regeneration of neurites by severing microtubules into small segments, and collapsin response mediator protein 5 (CRMP5) provides structural support and serves as a track for cargo transport by promoting microtubule polymerization. Nevertheless, how spastin and CRMP5 cooperate to regulate neurite outgrowth by controlling the microtubule dynamics needs to be elucidated. In our present study, spastin interacted with CRMP5 in vitro and in vivo. The binding domains for the spastin and CRMP5 interaction were the N‐terminal fragment of spastin (residues 270–328) and the C‐terminal fragment of CRMP5 (residues 472–564). Spastin and its truncation mutants, including the microtubule‐binding domain (MTBD) and ATPases associated with diverse cellular activities (AAA) domain, were necessary for the severing of microtubules. Furthermore, we demonstrated that microtubule polymerization of CRMP5 interfered with the microtubule‐severing function of spastin. Knocking down either spastin or CRMP5 inhibited neurite outgrowth in hippocampal neurons. However, co‐transfected spastin and CRMP5 promoted the outgrowth of neurites including dendrites and axons. Taken together, our data support a model in which the spastin interaction with CRMP5 promotes neurite outgrowth by controlling the microtubule dynamics.