Vinculin is required for neuronal mechanosensing but not for axon outgrowth

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

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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.
Original languageEnglish
Article number112805
JournalExperimental Cell Research
Early online date4 Sept 2021
DOIs
Publication statusPublished - 4 Sept 2021

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