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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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.

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Animals, Axons, CCAAT-Enhancer-Binding Proteins, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Guanine Nucleotide Exchange Factors, Intracellular Signaling Peptides and Proteins, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, Protein Biosynthesis, Protein-Serine-Threonine Kinases, RNA Stability, Synapses

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https://hdl.handle.net/10161/10619

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10.1016/j.cell.2009.06.023

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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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