PlexinA3 Interacts with CRMP2 to Mediate Sema3A Signalling During Dendritic Growth in Cultured Cerebellar Granule Neurons
PlexinA3 Interacts with CRMP2 to Mediate Sema3A Signalling During Dendritic Growth in Cultured Cerebellar Granule Neurons
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PlexinA3 与 CRMP2 相互作用，在培养的小脑颗粒神经元的树突生长过程中介导 Sema3A 信号传导
DOI：
10.1016/j.neuroscience.2020.02.008
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发表时间：
2020-05-10
期刊：
影响因子：
3.3
通讯作者：
Tan, Minghui
中科院分区：
文献类型：
--
作者：
Jiang, Tao;Zhang, Guowei;Tan, Minghui
丛状蛋白家族蛋白在树枝发育过程中介导信号素信号传递。然而，PlexinA3在培养的小脑颗粒神经元(CGN)树突生长中的作用尚不清楚。我们发现丛状蛋白A3与CRMP2(崩塌反应介质蛋白2)共定位于树突状突起。免疫沉淀和谷胱甘肽转移酶下拉实验表明，丛状蛋白A3的胞内RAS结合区直接与CRMP2相互作用。PlexinA3是CGN树突生长的必要条件和充分条件，因为PlexinA3的基因敲除减少了，但其过表达增加了树突的长度和树突顶端的数量。这些增加随着CRMP2的过度表达而增强，而在CRMP2被敲除后被取消，这表明CRMP2是下游的效应因子。此外，PlexinA3/CRMP2信号有助于Sema3A控制的树突生长。综上所述，这些数据确定了信号素调控培养的CGN树突状细胞生长的新的PlexinA3/CRMP2途径。(C)2020作者。爱思唯尔有限公司代表伊布罗出版。
Plexin family proteins mediate semaphorin signalling during dendritic arbour development. However, the role of PlexinA3 in the growth of dendrites of cultured cerebellar granule neurons (CGNs) is not known. We found that PlexinA3 colocalizes with CRMP2 (collapsin response mediator protein 2) in dendritic shafts. Immunoprecipitation and glutathione transferase pulldown assays showed that the intracellular Ras-binding domain of PlexinA3 directly interacts with CRMP2. PlexinA3 was necessary and sufficient for the growth of CGN dendrites, as genetic knockdown of PlexinA3 reduced but its overexpression increased dendritic lengths and dendritic tip numbers. These increases were enhanced with CRMP2 overexpression and abolished with CRMP2 knockdown, indicating that CRMP2 is the downstream effector. Furthermore, PlexinA3/CRMP2 signalling contributed to Sema3A-controlled dendritic growth. Together, these data identify a novel PlexinA3/CRMP2 pathway in semaphorin-regulated growth of cultured CGN dendrites. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of IBRO.