Reference - Detail
RRC ID | 4486 |
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Author | Yan D, Wu Z, Chisholm AD, Jin Y. |
Title | The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration. |
Journal | Cell |
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. |
Volume | 138(5) |
Pages | 1005-18 |
Published | 2009-9-4 |
DOI | 10.1016/j.cell.2009.06.023 |
PII | S0092-8674(09)00723-5 |
PMID | 19737525 |
PMC | PMC2772821 |
MeSH | Animals Axons / metabolism CCAAT-Enhancer-Binding Proteins / metabolism Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Guanine Nucleotide Exchange Factors / metabolism Intracellular Signaling Peptides and Proteins / metabolism MAP Kinase Kinase Kinases / metabolism* MAP Kinase Signaling System Protein Biosynthesis Protein Serine-Threonine Kinases / metabolism RNA Stability* Synapses* |
IF | 38.637 |
Times Cited | 210 |
WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
Resource | |
C.elegans | tm2807 tm2927 |