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bioRxiv · 10.1101/618686

Basement membrane regulates fibronectin organization using sliding focal adhesions driven by a contractile winch

Lu, J.·Doyle, A. D.·Yoshinari, S.·Wang, S.·Bodendorfer, M. A.·Zheng, M.·Yamada, K.
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Abstract

We have discovered that basement membrane and its major components can induce rapid, strikingly robust fibronectin organization. In this new matrix assembly mechanism, 5{beta}1 integrin-based focal adhesions slide actively on the underlying matrix towards the ventral cell center through the dynamic shortening of myosin IIA-associated actin stress fibers to drive rapid fibronectin fibrillogenesis distal to the adhesion. This mechanism contrasts with classical fibronectin assembly based on stable/fixed-position focal adhesions containing V{beta}3 integrins plus 5{beta}1 integrin translocation into proximal fibrillar adhesions. On basement membrane components, these sliding focal adhesions contain standard focal adhesion constituents but completely lack classical V{beta}3 integrins. Instead, peripheral 3{beta}1 or 2{beta}1 adhesions mediate initial cell attachment, but over time are switched to 5{beta}1 integrin-based sliding focal adhesions to assemble fibronectin matrix. This basement membrane-triggered mechanism produces rapid fibronectin fibrillogenesis, providing a mechanistic explanation for the well-known widespread accumulation of fibronectin at many organ basement membranes.

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Lu, J., Doyle, A. D., Yoshinari, S., Wang, S., Bodendorfer, M. A., Zheng, M., Yamada, K.. 2019-04-25. Basement membrane regulates fibronectin organization using sliding focal adhesions driven by a contractile winch. https://doi.org/10.1101/618686

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