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The p38 MAP kinase pathway modulates the hypoxia response and glutamate receptor trafficking in aging neurons

  1. Eun Chan Park
  2. Christopher Rongo  Is a corresponding author
  1. Rutgers The State University of New Jersey, United States
Research Article
  • Cited 10
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Cite this article as: eLife 2016;5:e12010 doi: 10.7554/eLife.12010

Abstract

Neurons are sensitive to low oxygen (hypoxia) and employ a conserved pathway to combat its effects. Here, we show that p38 MAP Kinase (MAPK) modulates this hypoxia response pathway in C. elegans. Mutants lacking p38 MAPK components pmk-1 or sek-1 resemble mutants lacking the hypoxia response component and prolyl hydroxylase egl-9, with impaired subcellular localization of Mint orthologue LIN-10, internalization of glutamate receptor GLR-1, and depression of GLR-1-mediated behaviors. Loss of p38 MAPK impairs EGL-9 protein localization in neurons and activates the hypoxia-inducible transcription factor HIF-1, suggesting that p38 MAPK inhibits the hypoxia response pathway through EGL-9. As animals age, p38 MAPK levels decrease, resulting in GLR-1 internalization; this age-dependent downregulation can be prevented through either p38 MAPK overexpression or removal of CDK-5, an antagonizing kinase. Our findings demonstrate that p38 MAPK inhibits the hypoxia response pathway and determines how aging neurons respond to hypoxia through a novel mechanism.

Article and author information

Author details

  1. Eun Chan Park

    The Waksman Institute, Department of Genetics, Rutgers The State University of New Jersey, New Jersey, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Christopher Rongo

    The Waksman Institute, Department of Genetics, Rutgers The State University of New Jersey, New Jersey, United States
    For correspondence
    rongo@waksman.rutgers.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Jan-Marino Ramirez, Seattle Children's Research Institute and University of Washington, United States

Publication history

  1. Received: October 1, 2015
  2. Accepted: January 4, 2016
  3. Accepted Manuscript published: January 5, 2016 (version 1)
  4. Version of Record published: February 23, 2016 (version 2)

Copyright

© 2016, Park & Rongo

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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