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

• Main Authors: Lizhen Chen, Marian Chuang, Thijs Koorman, Mike Boxem, Yishi Jin, Andrew D Chisholm
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2015-09-01
• Series: eLife
• Subjects: microtubules; axon regeneration; Patronin
• Online Access: https://elifesciences.org/articles/08695

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.