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Semaphorin 3A activates the guanosine triphosphatase Rab5 to promote growth cone collapse and organize callosal axon projections | |
2014 | |
发表期刊 | SCIENCE SIGNALING |
ISSN | 1945-0877 |
EISSN | 1937-9145 |
卷号 | 7期号:340 |
发表状态 | 已发表 |
DOI | 10.1126/scisignal.2005334 |
摘要 | Axon guidance (pathfinding) wires the brain during development and is regulated by various attractive and repulsive cues. Semaphorin 3A (Sema3A) is a repulsive cue, inducing the collapse of axon growth cones. In the mammalian forebrain, the corpus callosum is the major commissure that transmits information flow between the two hemispheres, and contralateral axons assemble into well-defined tracts. We found that the patterning of callosal axon projections in rodent layer II and III (L2/3) cortical neurons in response to Sema3A was mediated by the activation of Rab5, a small guanosine triphosphatase (GTPase) that mediates endocytosis, through the membrane fusion protein Rabaptin-5 and the Rab5 guanine nucleotide exchange factor (GEF) Rabex-5. Rabaptin-5 bound directly to Plexin-A1 in the Sema3A receptor complex [ an obligate heterodimer formed by Plexin-A1 and neuropilin 1 (NP1)]; Sema3A enhanced this interaction in cultured neurons. Rabaptin-5 bridged the interaction between Rab5 and Plexin-A1. Sema3A stimulated endocytosis from the cell surface of callosal axon growth cones. In utero electroporation to reduce Rab5 or Rabaptin-5 impaired axon fasciculation or caused mistargeting of L2/3 callosal projections in rats. Overexpression of Rabaptin-5 or Rab5 rescued the defective callosal axon fasciculation or mistargeting of callosal axons caused by the loss of Sema3A-Plexin-A1 signaling in rats expressing dominant-negative Plexin-A1 or in NP1-deficient mice. Thus, our findings suggest that Rab5, its effector Rabaptin-5, and its regulator Rabex-5 mediate Sema3A-induced axon guidance during brain development. |
URL | 查看原文 |
收录类别 | SCI |
WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
WOS类目 | Biochemistry & Molecular Biology ; Cell Biology |
WOS记录号 | WOS:000341425900001 |
WOS关键词 | SMALL GTPASE RAB5 ; RECEPTOR ; NEUROPILIN ; PROTEIN ; ENDOCYTOSIS ; RABAPTIN-5 ; GUIDANCE ; NEURONS ; L1 ; SIGNALS |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/120335 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Luo, Zhen-Ge |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, State Key Lab Neurosci, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Natl Ctr Nanosci & Technol, Key Lab Biol Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China 3.Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA |
推荐引用方式 GB/T 7714 | Wu, Kong-Yan,He, Miao,Hou, Qiong-Qiong,et al. Semaphorin 3A activates the guanosine triphosphatase Rab5 to promote growth cone collapse and organize callosal axon projections[J]. SCIENCE SIGNALING,2014,7(340). |
APA | Wu, Kong-Yan.,He, Miao.,Hou, Qiong-Qiong.,Sheng, Ai-Li.,Yuan, Lei.,...&Luo, Zhen-Ge.(2014).Semaphorin 3A activates the guanosine triphosphatase Rab5 to promote growth cone collapse and organize callosal axon projections.SCIENCE SIGNALING,7(340). |
MLA | Wu, Kong-Yan,et al."Semaphorin 3A activates the guanosine triphosphatase Rab5 to promote growth cone collapse and organize callosal axon projections".SCIENCE SIGNALING 7.340(2014). |
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