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Elife. 2015 Sep 4;4. doi: 10.7554/eLife.08695.

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

Author information

1
Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, United States.
2
University of California, San Diego, La Jolla, United States.
3
Department of Biology, Utrecht University, Utrecht, Netherlands.
4
Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, United States.

Abstract

Axon injury triggers a series of changes in the axonal cytoskeleton that are prerequisites for effective axon regeneration. In Caenorhabditis elegans the signaling protein Exchange Factor for ARF-6 (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.

KEYWORDS:

C. elegans; Patronin; axon regeneration; developmental biology; microtubules; neuroscience; stem cells

PMID:
26339988
PMCID:
PMC4596636
DOI:
10.7554/eLife.08695
[Indexed for MEDLINE]
Free PMC Article

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