DLK-1激酶促进秀丽隐杆线虫突触中的mRNA稳定性和局部翻译以及轴突再生。
The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration.
作者信息
Yan Dong, Wu Zilu, Chisholm Andrew D, Jin Yishi
机构信息
Division of Biological Sciences, Section of Neurobiology, University of California, San Diego, La Jolla, CA 92093, USA.
出版信息
Cell. 2009 Sep 4;138(5):1005-18. doi: 10.1016/j.cell.2009.06.023.
Abstract
Growth cone guidance and synaptic plasticity involve dynamic local changes in proteins at axons and dendrites. The Dual-Leucine zipper Kinase MAPKKK (DLK) has been previously implicated in synaptogenesis and axon outgrowth in C. elegans and other animals. Here we show that in C. elegans DLK-1 regulates not only proper synapse formation and axon morphology but also axon regeneration by influencing mRNA stability. DLK-1 kinase signals via a MAPKAP kinase, MAK-2, to stabilize the mRNA encoding CEBP-1, a bZip protein related to CCAAT/enhancer-binding proteins, via its 3'UTR. Inappropriate upregulation of cebp-1 in adult neurons disrupts synapses and axon morphology. CEBP-1 and the DLK-1 pathway are essential for axon regeneration after laser axotomy in adult neurons, and axotomy induces translation of CEBP-1 in axons. Our findings identify the DLK-1 pathway as a regulator of mRNA stability in synapse formation and maintenance and also in adult axon regeneration.
摘要
生长锥导向和突触可塑性涉及轴突和树突中蛋白质的动态局部变化。双亮氨酸拉链激酶丝裂原活化蛋白激酶激酶激酶（DLK）先前已被证明参与秀丽隐杆线虫和其他动物的突触形成和轴突生长。在这里，我们表明，在秀丽隐杆线虫中，DLK-1不仅通过影响mRNA稳定性来调节正确的突触形成和轴突形态，还调节轴突再生。DLK-1激酶通过丝裂原活化蛋白激酶相关激酶MAK-2发出信号，通过其3'非翻译区稳定编码CEBP-1的mRNA，CEBP-1是一种与CCAAT/增强子结合蛋白相关的bZip蛋白。成年神经元中cebp-1的不适当上调会破坏突触和轴突形态。CEBP-1和DLK-1途径对于成年神经元激光切断轴突后的轴突再生至关重要，并且轴突切断会诱导轴突中CEBP-1的翻译。我们的研究结果表明，DLK-1途径是突触形成、维持以及成年轴突再生过程中mRNA稳定性的调节因子。
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Axon regeneration requires a conserved MAP kinase pathway.轴突再生需要一条保守的丝裂原活化蛋白激酶信号通路。
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