title: The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration.
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.
authors.affiliation: Division of Biological Sciences, Section of Neurobiology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Yan
authors.forename: Zilu
authors.initials: Z
authors.lastname: Wu
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Chisholm
authors.forename: Yishi
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020871:RNA Stability; D013569:Synapses; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D029742:Caenorhabditis elegans Proteins; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C409634:RPM-1 protein, C elegans; C498050:DLK-1 protein, C elegans