The netrin receptor UNC-40/DCC stimulates axon attraction and outgrowth through enabled and, in parallel, Rac and UNC-115/AbLIM
The netrin receptor UNC-40/DCC stimulates axon attraction and outgrowth through enabled and, in parallel, Rac and UNC-115/AbLIM
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DOI：
10.1016/s0896-6273(02)01149-2
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发表时间：
2003-01-09
期刊：
影响因子：
16.2
通讯作者：
Bargmann, CI
中科院分区：
文献类型：
--
作者：
Gitai, Z;Yu, TW;Bargmann, CI
Netrins促进轴突生长，并通过DCC/β-40受体转化。为了表征Netrin信号传导，我们产生了功能获得性MYR：：MYR-40分子。MYR：：MYR-40导致轴突导向缺陷、过度的轴突分支以及过度的轴突和细胞体生长。这些缺陷被ced-10（一种Rac GT3）、unc-34（一种使能同源物）和unc-115（一种推定的肌动蛋白结合蛋白）中的功能丧失突变抑制。CED-10、UNC-34和UNC-115也在内源性UNC-40信号传导中起作用。我们的研究结果表明，使能功能的轴突吸引以及轴突排斥。β-40具有两个保守的胞质基序，它们介导不同的下游途径：CED-10、β-115和β-40 P2基序在一个途径中起作用，β-34和β-40 P1基序在另一个途径中起作用。因此，α-40可能作为一个支架传递几个独立的信号到肌动蛋白细胞骨架。
Netrins promote axon outgrowth and turning through DCC/UNC-40 receptors. To characterize Netrin signaling, we generated a gain-of-function UNC-40 molecule, MYR::UNC-40. MYR::UNC-40 causes axon guidance defects, excess axon branching, and excessive axon and cell body outgrowth. These defects are suppressed by loss-of-function mutations in ced-10 (a Rac GTPase), unc-34 (an Enabled homolog), and unc-115 (a putative actin binding protein). ced-10, unc-34, and unc-115 also function in endogenous unc-40 signaling. Our results indicate that Enabled functions in axonal attraction as well as axon repulsion. UNC-40 has two conserved cytoplasmic motifs that mediate distinct downstream pathways: CED-10, UNC-115, and the UNC-40 P2 motif act in one pathway, and UNC-34 and the UNC-40 P1 motif act in the other. Thus, UNC-40 might act as a scaffold to deliver several independent signals to the actin cytoskeleton.