Abstract
Axon growth requires coordination of the actin cytoskeleton by actin-binding proteins in the extending neurites. Vinculin is a major constituent of focal adhesion but its role in neuronal migration and axon growth is poorly understood. We found that vinculin deletion in mouse neocortical neurons attenuated axon growth both in vitro and in vivo. Using different functional mutants of vinculin, we found that expression of a constitutively active vinculin significantly enhanced axon growth while the head-neck domain had a moderate inhibitory effect. Interesting, we found that vinculin-talin interaction was dispensable for axon growth and neuronal migration. Strikingly, expression of the tail domain delayed migration, increased branching and stunted axon. Inhibition of the Arp2/3 complex or abolishing the tail domain interaction with actin completely reversed the branching phenotype caused by tail domain expression without affecting axon length. Super-resolution microscopy showed increased mobile fraction of actin in tail domain expressing neurons. Our results provide novel insights into the role of vinculin and its functional domains in regulating neuronal migration and axon growth.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Revised some of the results and the discussion section. Some figure panels in Figures 2 and 5 were replaced.
