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

ELife
Lizhen ChenAndrew D Chisholm

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.

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Citations

May 7, 2016·Neuron·Zhigang He, Yishi Jin
Oct 26, 2016·Brain Research Bulletin·André VoelzmannAndreas Prokop
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Nov 8, 2017·Proceedings of the National Academy of Sciences of the United States of America·Atrayee BasuAnindya Ghosh-Roy
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Mar 19, 2019·Annual Review of Neuroscience·Claire E Richardson, Kang Shen
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Jan 17, 2021·Brain and Behavior·Bente Kjaer LyngsøeBodil Hammer Bech
Nov 17, 2021·Neural Regeneration Research·Bart Nieuwenhuis, Richard Eva

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Methods Mentioned

BETA
GTPases
transgenic
two-hybrid
co-immunoprecipitation
immunoprecipitation
PCR
genotyping
Transfection

Software Mentioned

Metamorph
Mos
Zeiss
GraphPad
WormTracker
SCI
Prism

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