MAX-1, a novel PH/MyTH4/FERM domain cytoplasmic protein implicated in netrin-mediated axon repulsion
MAX-1, a novel PH/MyTH4/FERM domain cytoplasmic protein implicated in netrin-mediated axon repulsion
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DOI：
10.1016/s0896-6273(02)00672-4
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发表时间：
2002-05-16
期刊：
影响因子：
16.2
通讯作者：
Jin, YS
中科院分区：
文献类型：
--
作者：
Huang, X;Cheng, HJ;Jin, YS
netrin β-6通过单独激活β-5受体或与β-40/DCC受体组合激活β-5受体来排斥运动轴突。在C.在运动神经元轴突投射中表现出部分缺陷的Elegans突变体中，我们分离了MAX-1基因（运动神经元轴突引导所需的）。MAX-1功能丧失突变导致完全渗透但可变的轴突导向缺陷。unc-5和unc-6的突变，而不是unc-40的突变，主要增强max-1的突变表型，而unc-5或unc-6的过表达，而不是unc-40的过表达，绕过了max-1的要求。MAX-1蛋白含有PH、MyTH 4和FERM结构域，并且似乎定位于神经元过程。人MAX-1和UNC 5 H2共定位于转染细胞的离散亚细胞区域。我们的研究结果表明，MAX-1在netrin诱导的轴突排斥中可能通过调节β-5受体信号通路发挥作用。
The netrin UNC-6 repels motor axons by activating the UNC-5 receptor alone or in combination with the UNC-40/DCC receptor. In a genetic screen for C. elegans mutants exhibiting partial defects in motor axon projections, we isolated the max-1 gene (required for motor neuron axon guidance). max-1 loss-of-function mutations cause fully penetrant but variable axon guidance defects. Mutations in unc-5 and unc-6, but not in unc-40 dominantly enhance the mutant phenotypes of max-1, whereas overexpression of unc-5 or unc-6, but not of unc-40, bypasses the requirement for max-1. MAX-1 proteins contain PH, MyTH4, and FERM domains and appear to be localized to neuronal processes. Human MAX-1 and UNC5H2 colocalize in discrete subcellular regions of transfected cells. Our results suggest a possible role for MAX-1 in netrin-induced axon repulsion by modulating the UNC-5 receptor signaling pathway.