Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase
- Howard Hughes Medical Institute, University of California, San Diego, United States
- University of California, San Diego, United States
- 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.
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© 2015, Chen et al.
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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
