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Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase RPM-1 is required for presynaptic development

Academic Article
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Overview

authors

  • Nakata, K.
  • Abrams, B.
  • Grill, Brock
  • Goncharov, A.
  • Huang, X.
  • Chisholm, A. D.
  • Jin, Y. S.

publication date

  • February 2005

journal

  • Cell  Journal

abstract

  • Synapses display a stereotyped ultrastructural organization, commonly containing a single electron-dense presynaptic density surrounded by a cluster of synaptic vesicles. The mechanism controlling subsynaptic proportion is not understood. Loss of function in the C. elegans rpm-1 gene, a putative RING finger/E3 ubiquitin ligase, causes disorganized presynaptic cytoarchitecture. RPM-1 is localized to the presynaptic periactive zone. We report that RPM-1 negatively regulates a p38 MAP kinase pathway composed of the dual leucine zipper-bearing MAPKKK DLK-1, the MAPKK MKK-4, and the p38 MAP kinase PMK-3. Inactivation of this pathway suppresses rpm-1 loss of function phenotypes, whereas overexpression or constitutive activation of this pathway causes synaptic defects resembling rpm-1(lf) mutants. DLK-1, like RPM-1, is localized to the periactive zone. DLK-1 protein levels are elevated in rpm-1 mutants. The RPM-1 RING finger can stimulate ubiquitination of DLK-1. Our data reveal a presynaptic role of a previously unknown p38 MAP kinase cascade.

subject areas

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Cell Differentiation
  • Guanine Nucleotide Exchange Factors
  • MAP Kinase Kinase Kinases
  • MAP Kinase Signaling System
  • Microscopy, Electron, Transmission
  • Mitogen-Activated Protein Kinases
  • Mutation
  • Nervous System
  • Presynaptic Terminals
  • Protein Structure, Tertiary
  • Ubiquitin
  • p38 Mitogen-Activated Protein Kinases
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Identity

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2004.12.017

PubMed ID

  • 15707898
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Additional Document Info

start page

  • 407

end page

  • 420

volume

  • 120

issue

  • 3

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