PlexinA1 is a new Slit receptor and mediates axon guidance function of Slit C-terminal fragments
PlexinA1 is a new Slit receptor and mediates axon guidance function of Slit C-terminal fragments
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DOI：
10.1038/nn.3893
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发表时间：
2015-01-01
影响因子：
25
通讯作者：
Castellani, Valerie
中科院分区：
文献类型：
--
作者：
Delloye-Bourgeois, Celine;Jacquier, Arnaud;Castellani, Valerie
Robo-Slit和丛蛋白-脑信号蛋白信号转导参与各种发育和致病过程。在脊髓中的连合轴突引导期间，通过Semaphorin 3B和Slits的化学排斥控制中线穿越。Slit处理产生结合Robo 1和Robo 2受体并介导Slit排斥活性的N-末端片段（SlitN），以及具有未知受体和生物活性的C-末端片段（SlitC）。我们确定PlexinA 1作为Slit受体，并发现它特异性结合C-末端Slit片段，并独立于Robos和Neuropilins转导SlitC信号。在脊髓提取物中检测到丛蛋白A1-SlitC复合物，并且离体，SlitC与丛蛋白A1的结合引起排斥性连合反应。对各种配体和受体敲除小鼠的分析表明，丛蛋白A1-Slit和Robo-Slit信号在连合轴突引导过程中具有互补作用。因此，丛蛋白A1介导脑信号蛋白和Slit信号传导，Slit处理产生两个活性片段，每个片段通过特定受体发挥不同的作用。
Robo-Slit and Plexin-Semaphorin signaling participate in various developmental and pathogenic processes. During commissural axon guidance in the spinal cord, chemorepulsion by Semaphorin3B and Slits controls midline crossing. Slit processing generates an N-terminal fragment (SlitN) that binds to Robo1 and Robo2 receptors and mediates Slit repulsive activity, as well as a C-terminal fragment (SlitC) with an unknown receptor and bioactivity. We identified PlexinA1 as a Slit receptor and found that it binds the C-terminal Slit fragment specifically and transduces a SlitC signal independently of the Robos and the Neuropilins. PlexinA1-SlitC complexes are detected in spinal cord extracts, and ex vivo, SlitC binding to PlexinA1 elicits a repulsive commissural response. Analysis of various ligand and receptor knockout mice shows that PlexinA1-Slit and Robo-Slit signaling have complementary roles during commissural axon guidance. Thus, PlexinA1 mediates both Semaphorin and Slit signaling, and Slit processing generates two active fragments, each exerting distinct effects through specific receptors.