PT  - JOURNAL ARTICLE
AU  - Pranay Mandal
AU  - Vivek Belapurkar
AU  - Deepak Nair
AU  - Narendrakumar Ramanan
TI  - Vinculin mediated axon growth requires interaction with actin but not talin
AID  - 10.1101/2020.06.29.177758
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.29.177758
4099  - http://biorxiv.org/content/early/2020/06/29/2020.06.29.177758.short
4100  - http://biorxiv.org/content/early/2020/06/29/2020.06.29.177758.full
AB  - Axon growth requires coordination of the actin cytoskeleton by actin-binding proteins in the growth cones of the extending neurites. The actin-binding protein vinculin (Vcl) 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 functional mutants of vinculin, we found that various domains of vinculin affect cell migration and axon growth differently. While expression of a constitutively active vinculin significantly enhanced axon growth, the head-neck domain had a moderate inhibitory effect. Contrary to previous findings, vinculintalin interaction was dispensable for axon growth and neuronal migration. Strikingly, expression of the tail domain delayed neuronal migration and caused increased branching, enlarged soma and highly stunted axon both in vitro and in vivo. Inhibition of the Arp2/3 complex completely reversed the branching phenotype caused by tail domain expression without affecting axon length. Similarly, abolishing the tail domain interaction with actin reversed the enlarged cell soma and branching phenotypes but not 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 StatementThe authors have declared no competing interest.