De Yao Wang
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
Cristina Melero
Ashwaq Albaraky
Paul Atherton
Karin A. Jansen
Andrea Dimitracopoulos
FEDERICO DAJAS-BAILADOR F.Dajas-Bailador@nottingham.ac.uk
Associate Professor
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#! |
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