UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways
UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways
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DOI：
10.1038/nn.2256
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发表时间：
2009-02-01
影响因子：
25
通讯作者：
Culotti, Joseph G.
中科院分区：
文献类型：
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作者：
MacNeil, Lesley T.;Hardy, W. Rod;Culotti, Joseph G.
β-5受体通过β-40依赖性（β-5 + β-40）和独立性（β-5单独）信号传导途径介导轴突对β-6/netrin的排斥。已经表明，β-40依赖性信号传导是β-6/netrin的长程排斥所必需的;然而，用于调节不同β-5信号传导途径的机制知之甚少。我们发现C. elegans转化生长因子β（TGF-β）家族配体β 1 -129，与β 2 -6/netrin分级相反，不依赖于典型的TGF-β受体而发挥调节β 1 -5细胞应答的功能。我们的观察结果表明，通过与α-5受体的相互作用，α-129通过增强α-5 + α-40信号传导而促进α-6的长距离排斥引导，而代价是α-5单独的信号传导。这增加了生长锥对β-6/netrin的设定点敏感性，因为它们同时向上迁移β-129梯度和向下迁移β-6梯度。相反分级的细胞外信号之间的类似调节相互作用可能是引导细胞和轴突迁移的共同主题。
The UNC-5 receptor mediates axon repulsion from UNC-6/netrin through UNC-40 dependent (UNC-5 + UNC-40) and independent (UNC-5 alone) signaling pathways. It has been shown that UNC-40-dependent signaling is required for long-range repulsion of UNC-6/netrin; however, the mechanisms used to regulate distinct UNC-5 signaling pathways are poorly understood. We found that the C. elegans transforming growth factor beta (TGF-beta) family ligand UNC-129, graded opposite to UNC-6/netrin, functions independent of the canonical TGF-beta receptors to regulate UNC-5 cellular responses. Our observations indicates that UNC-129 facilitates long-range repulsive guidance of UNC-6 by enhancing UNC-5 + UNC-40 signaling at the expense of UNC-5 alone signaling through interaction with the UNC-5 receptor. This increases the set point sensitivity of growth cones to UNC-6/netrin as they simultaneously migrated up the UNC-129 gradient and down the UNC-6 gradient. Similar regulatory interactions between oppositely graded extracellular cues may be a common theme in guided cell and axon migrations.