Vinculin-mediated axon growth requires interaction with actin but not talin in mouse neocortical neurons

The actin-binding protein vinculin is a major constituent of focal adhesion, but its role in neuronal development is poorly understood. We found that vinculin deletion in mouse neocortical neurons attenuated axon growth both in vitro and in vivo. Using functional mutants, we found that expression of a constitutively active vinculin significantly enhanced axon growth while the head-neck domain had an inhibitory effect. Interestingly, 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 mobility 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.

Automated summary

The actin-binding protein vinculin plays a critical role in axon growth and neuronal migration, with different functional domains having distinct effects on these processes. The interaction between vinculin and talin is found to be dispensable for axon growth and neuronal migration. Expression of the tail domain of vinculin delays migration, increases branching, and stunts axon growth.