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Vinculin is required for neuronal mechanosensing but not for axon outgrowth

Wang, De Yao; Melero, Cristina; Albaraky, Ashwaq; Atherton, Paul; Jansen, Karin A.; Dimitracopoulos, Andrea; Dajas-Bailador, Federico; Reid, Adam; Franze, Kristian; Ballestrem, Christoph

Authors

De Yao Wang

Cristina Melero

Ashwaq Albaraky

Paul Atherton

Karin A. Jansen

Andrea Dimitracopoulos

Adam Reid

Kristian Franze

Christoph Ballestrem



Abstract

Integrin receptors are transmembrane proteins that bind to the extracellular matrix (ECM). In most animal cell types integrins cluster together with adaptor proteins at focal adhesions that sense and respond to external mechanical signals. In the central nervous system (CNS), ECM proteins are sparsely distributed, the tissue is comparatively soft and neurons do not form focal adhesions. Thus, how neurons sense tissue stiffness is currently poorly understood. Here, we found that integrins and the integrin-associated proteins talin and focal adhesion kinase (FAK) are required for the outgrowth of neuronal processes. Vinculin, however, whilst not required for neurite outgrowth was a key regulator of integrin-mediated mechanosensing of neurons. During growth, growth cones of axons of CNS derived cells exerted dynamic stresses of around 10–12 Pa on their environment, and axons grew significantly longer on soft (0.4 kPa) compared to stiff (8 kPa) substrates. Depletion of vinculin blocked this ability of growth cones to distinguish between soft and stiff substrates. These data suggest that vinculin in neurons acts as a key mechanosensor, involved in the regulation of growth cone motility.

Citation

Wang, D. Y., Melero, C., Albaraky, A., Atherton, P., Jansen, K. A., Dimitracopoulos, A., …Ballestrem, C. (2021). Vinculin is required for neuronal mechanosensing but not for axon outgrowth. Experimental Cell Research, 407(2), Article 112805. https://doi.org/10.1016/j.yexcr.2021.112805

Journal Article Type Article
Acceptance Date Aug 21, 2021
Online Publication Date Sep 4, 2021
Publication Date Oct 15, 2021
Deposit Date Nov 10, 2021
Journal Experimental Cell Research
Print ISSN 0014-4827
Electronic ISSN 1090-2422
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 407
Issue 2
Article Number 112805
DOI https://doi.org/10.1016/j.yexcr.2021.112805
Keywords Cell Biology
Public URL https://nottingham-repository.worktribe.com/output/6244992
Publisher URL https://www.sciencedirect.com/science/article/pii/S001448272100358X?via%3Dihub#!