The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration.
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2009-09-04
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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.
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Yan, Dong, Zilu Wu, Andrew D Chisholm and Yishi Jin (2009). The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration. Cell, 138(5). pp. 1005–1018. 10.1016/j.cell.2009.06.023 Retrieved from https://hdl.handle.net/10161/10619.
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Dong Yan
we are interested in understanding the molecular mechanisms underlying neural circuit formation during development and degeneration in aging. In my lab, We use a free-living tiny roundworm, called Caenorhabditis elegans, as a model. The defined cell lineage, completely mapped connectome and rapid life cycle of this organism greatly facilitate investigating nervous system at the subcellular resolution. Combining classic genetic analysis with in vivo live imaging technique and molecular and cellular manipulations, we are discovering conserved mechanisms playing key roles in neural circuit formation, gap junction dynamics and neurodegeneration
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