The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration.
| dc.contributor.author | Yan, Dong | |
| dc.contributor.author | Wu, Zilu | |
| dc.contributor.author | Chisholm, Andrew D | |
| dc.contributor.author | Jin, Yishi | |
| dc.coverage.spatial | United States | |
| dc.date.accessioned | 2015-09-16T21:42:38Z | |
| dc.date.issued | 2009-09-04 | |
| dc.description.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. | |
| dc.identifier | ||
| dc.identifier | S0092-8674(09)00723-5 | |
| dc.identifier.eissn | 1097-4172 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Elsevier BV | |
| dc.relation.ispartof | Cell | |
| dc.relation.isversionof | 10.1016/j.cell.2009.06.023 | |
| dc.subject | Animals | |
| dc.subject | Axons | |
| dc.subject | CCAAT-Enhancer-Binding Proteins | |
| dc.subject | Caenorhabditis elegans | |
| dc.subject | Caenorhabditis elegans Proteins | |
| dc.subject | Guanine Nucleotide Exchange Factors | |
| dc.subject | Intracellular Signaling Peptides and Proteins | |
| dc.subject | MAP Kinase Kinase Kinases | |
| dc.subject | MAP Kinase Signaling System | |
| dc.subject | Protein Biosynthesis | |
| dc.subject | Protein-Serine-Threonine Kinases | |
| dc.subject | RNA Stability | |
| dc.subject | Synapses | |
| dc.title | The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration. | |
| dc.type | Journal article | |
| pubs.author-url | ||
| pubs.begin-page | 1005 | |
| pubs.end-page | 1018 | |
| pubs.issue | 5 | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Duke Institute for Brain Sciences | |
| pubs.organisational-group | Institutes and Provost's Academic Units | |
| pubs.organisational-group | Molecular Genetics and Microbiology | |
| pubs.organisational-group | Neurobiology | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | University Institutes and Centers | |
| pubs.publication-status | Published | |
| pubs.volume | 138 |
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