Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase

  1. Lizhen Chen
  2. Marian Chuang
  3. Thijs Koorman
  4. Mike Boxem
  5. Yishi Jin
  6. Andrew D Chisholm  Is a corresponding author
  1. Howard Hughes Medical Institute, University of California, San Diego, United States
  2. University of California, San Diego, United States
  3. Utrecht University, Netherlands

Abstract

Axon injury triggers a series of changes in the axonal cytoskeleton that are prerequisites for effective axon regeneration. In C. elegans the signaling protein EFA-6 is a potent intrinsic inhibitor of axon regrowth. Here we show that axon injury triggers rapid EFA-6-dependent inhibition of axonal microtubule (MT) dynamics, concomitant with relocalization of EFA-6. EFA-6 relocalization and axon regrowth inhibition require a conserved 18-aa motif in its otherwise intrinsically disordered N-terminal domain. The EFA-6 N-terminus binds the MT-associated proteins TAC-1/Transforming-Acidic-Coiled-Coil, and ZYG-8/Doublecortin-Like-Kinase, both of which are required for regenerative growth cone formation, and which act downstream of EFA-6. After injury TAC-1 and EFA-6 transiently relocalize to sites marked by the MT minus end binding protein PTRN-1/Patronin. We propose that EFA-6 acts as a bifunctional injury-responsive regulator of axonal MT dynamics, acting at the cell cortex in the steady state and at MT minus ends after injury.

Article and author information

Author details

  1. Lizhen Chen

    Division of Biological Sciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Marian Chuang

    Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Thijs Koorman

    Department of Biology, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Mike Boxem

    Department of Biology, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Yishi Jin

    Division of Biological Sciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Andrew D Chisholm

    Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    For correspondence
    chisholm@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. K VijayRaghavan, National Centre for Biological Sciences, Tata Institute for Fundamental Research, India

Version history

  1. Received: May 14, 2015
  2. Accepted: September 3, 2015
  3. Accepted Manuscript published: September 4, 2015 (version 1)
  4. Version of Record published: October 8, 2015 (version 2)

Copyright

© 2015, Chen et al.

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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  1. Lizhen Chen
  2. Marian Chuang
  3. Thijs Koorman
  4. Mike Boxem
  5. Yishi Jin
  6. Andrew D Chisholm
(2015)
Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase
eLife 4:e08695.
https://doi.org/10.7554/eLife.08695

Share this article

https://doi.org/10.7554/eLife.08695

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