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UNC-129调节UNC-40依赖性和非依赖性UNC-5信号通路之间的平衡。

UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways.

作者信息

MacNeil Lesley T, Hardy W Rod, Pawson Tony, Wrana Jeffrey L, Culotti Joseph G

机构信息

Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.

出版信息

Nat Neurosci. 2009 Feb;12(2):150-5. doi: 10.1038/nn.2256. Epub 2009 Jan 25.

DOI:10.1038/nn.2256
PMID:19169249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2745997/
Abstract

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.

摘要

UNC-5受体通过UNC-40依赖（UNC-5 + UNC-40）和独立（仅UNC-5）信号通路介导轴突对UNC-6/网蛋白的排斥。已表明，UNC-40依赖信号对于UNC-6/网蛋白的长程排斥是必需的；然而，用于调节不同UNC-5信号通路的机制却知之甚少。我们发现，秀丽隐杆线虫转化生长因子β（TGF-β）家族配体UNC-129的梯度与UNC-6/网蛋白相反，其功能独立于经典TGF-β受体，以调节UNC-5细胞反应。我们的观察结果表明，UNC-129通过增强UNC-5 + UNC-40信号来促进UNC-6的长程排斥性导向，代价是通过与UNC-5受体相互作用而减少仅UNC-5的信号。当生长锥同时沿UNC-129梯度向上迁移和沿UNC-6梯度向下迁移时，这增加了生长锥对UNC-6/网蛋白的设定点敏感性。相反梯度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中的一个共同主题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1407/2745997/e29375e94e81/nihms103074f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1407/2745997/31f3fae2061f/nihms103074f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1407/2745997/967bc4cbde03/nihms103074f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1407/2745997/a08fe7b72198/nihms103074f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1407/2745997/26ebaa4b63b8/nihms103074f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1407/2745997/e29375e94e81/nihms103074f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1407/2745997/31f3fae2061f/nihms103074f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1407/2745997/967bc4cbde03/nihms103074f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1407/2745997/a08fe7b72198/nihms103074f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1407/2745997/26ebaa4b63b8/nihms103074f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1407/2745997/e29375e94e81/nihms103074f5.jpg

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