Journal
EXPERIMENTAL CELL RESEARCH
Volume 407, Issue 2, Pages -Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2021.112805
Keywords
-
Categories
Funding
- BBSRC
- EPSRC
- MRC
- Wellcome Trust
- Wellcome Trust [203128/Z/16/Z]
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/M020630/1]
- Hargreaves and Ball Trust
- Academy of Medical Sciences (AMS-SGCL7)
- European Research Council [772326]
- Alexander von Humboldt Foundation
- BBSRC [BB/M020630/1] Funding Source: UKRI
Ask authors/readers for more resources
Integrins and their associated proteins are essential for neuronal axon outgrowth, while vinculin plays a crucial role in integrin-mediated mechanosensing in neurons.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available