| RRC ID |
45536
|
| Author |
Chen L, Chuang M, Koorman T, Boxem M, Jin Y, Chisholm AD.
|
| Title |
Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase.
|
| Journal |
Elife
|
| 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.
|
| Volume |
4
|
| Published |
2015-9-4
|
| DOI |
10.7554/eLife.08695
|
| PMID |
26339988
|
| PMC |
PMC4596636
|
| MeSH |
Animals
Axons / physiology*
Caenorhabditis elegans / physiology*
Caenorhabditis elegans Proteins / metabolism*
Cell Cycle Proteins / metabolism*
Microtubules / metabolism*
Regeneration
|
| IF |
7.08
|
| Times Cited |
21
|
| Resource |
| C.elegans |
tm3124 |
