Vinculin mediated axon growth requires interaction with actin but not talin

Abstract

<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>. 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.</jats:p>

Anti-vinculin autoantibodies in systemic sclerosis: a step toward a novel biomarker?

“…The presence of anti-vinculin autoantibodies in SSc is consistent with prior studies which have implicated vinculin as an important regulator of the enteric nervous system. Vinculin is notably involved in neuronal migration and axon growth, and vinculin deletion from mouse neocortical neurons results in attenuation of axon growth in vivo [8]. One study found an inverse association between anti-vinculin autoantibody titers and the density of interstitial cells of Cajal (ICC) in the myenteric plexus of human stomach from patients with gastric cancer [9].…”