Research article summary (published 2 Sep 2009):

The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration.

Full 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.

Author information

Author/s: Yan, Dong (D); Wu, Zilu (Z); Chisholm, Andrew D (AD); Jin, Yishi (Y);

Affiliation: Division of Biological Sciences, Section of Neurobiology, University of California, San Diego, La Jolla, CA 92093, USA.

Grants: R01 NS35546 (Agency:NINDS NIH HHS) ; R01 NS57317 (Agency:NINDS NIH HHS) ; (Agency:Howard Hughes Medical Institute)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Cell (Cell), published in United States. (Language: eng)

Reference: 2009-Sep; vol 138 (issue 5) : pp 1005-18

Dates: Created 2009/09/09; Completed 2009/09/30; Revised 2009/11/05;

PMID: 19737525, status: MEDLINE (last retrieval date: 11/6/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Axons - metabolism CCAAT-Enhancer-Binding Proteins - metabolism Caenorhabditis elegans - genetics; metabolism Caenorhabditis elegans Proteins - metabolism Guanine Nucleotide Exchange Factors - metabolism Intracellular Signaling Peptides and Proteins - 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

Associated Chemicals: CCAAT-Enhancer-Binding Proteins (0) ; Caenorhabditis elegans Proteins (0) ; Guanine Nucleotide Exchange Factors (0) ; Intracellular Signaling Peptides and Proteins (0) ; RPM-1 protein, C elegans (0) ; MAP-kinase-activated kinase 2 (EC 2.7.1.-) ; DLK-1 protein, C elegans (EC 2.7.1.37) ; MAP Kinase Kinase Kinases (EC 2.7.1.37) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)

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