Semaphorin 3A activates the guanosine triphosphatase Rab5 to promote growth cone collapse and organize callosal axon projections

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	Semaphorin 3A activates the guanosine triphosphatase Rab5 to promote growth cone collapse and organize callosal axon projections
	Wu, KY ; He, M ; Hou, QQ ; Sheng, AL ; Yuan, L ; Liu, F ; Liu, WW ; Li, GP ; Jiang, XY ; Luo, ZG
刊名	SCIENCE SIGNALING
	2014
卷号	7 期号:340 页码:81-81
关键词	SMALL GTPASE RAB5 PERIPHERAL-NERVE PROJECTION ENDOCYTIC MEMBRANE-FUSION CORPUS-CALLOSUM CEREBRAL-CORTEX NEURONAL POLARIZATION CORTICAL PROJECTION IN-VITRO RECEPTOR NEUROPILIN
ISSN号	1945-0877
通讯作者	Luo, ZG (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, State Key Lab Neurosci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,zgluo@ion.ac.cn
英文摘要	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.
学科主题	Biochemistry & Molecular Biology ; Cell Biology
收录类别	SCI
资助信息	Key State Research Program [2014CB910203]; National Natural Science Foundation of China [31371063, 31330032, 31321091, 61327902, 21025520]; Knowledge Innovation Program of Shanghai Institutes for Biological Sciences; Chinese Academy of Sciences [2013KIP206]; NIH [R01GM074692]
语种	英语
公开日期	2014-12-15
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/2647]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Wu, KY,He, M,Hou, QQ,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):81-81.
APA	Wu, KY.,He, M.,Hou, QQ.,Sheng, AL.,Yuan, L.,...&Luo, ZG.(2014).Semaphorin 3A activates the guanosine triphosphatase Rab5 to promote growth cone collapse and organize callosal axon projections.SCIENCE SIGNALING,7(340),81-81.
MLA	Wu, KY,et al."Semaphorin 3A activates the guanosine triphosphatase Rab5 to promote growth cone collapse and organize callosal axon projections".SCIENCE SIGNALING 7.340(2014):81-81.