Basement Membrane Regulates Fibronectin Organization Using Sliding Focal Adhesions Driven by a Contractile Winch

• Published in: Developmental cell 2020-03, Vol.52 (5), p.631-646.e4
• Main Authors: Lu, Jiaoyang, Doyle, Andrew D., Shinsato, Yoshinari, Wang, Shaohe, Bodendorfer, Molly A., Zheng, Minhua, Yamada, Kenneth M.
• Format: Article
• Language: English
• Subjects: basement membrane; extracellular matrix; fibrillogenesis; fibronectin; focal adhesion; integrin; matrix assembly
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2020.01.007

We have discovered that basement membrane and its major components can induce rapid, strikingly robust fibronectin organization. In this new matrix assembly mechanism, α5β1 integrin-based focal adhesions slide actively on the underlying matrix toward 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 or fixed-position focal adhesions containing αVβ3 integrins plus α5β1 integrin translocation into proximal fibrillar adhesions. On basement membrane components, these sliding focal adhesions contain standard focal adhesion constituents but completely lack classical αVβ3 integrins. Instead, peripheral α3β1 or α2β1 adhesions mediate initial cell attachment but over time are switched to α5β1 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. [Display omitted] •Basement membrane matrix molecules can rapidly induce robust fibronectin assembly•A contractile actomyosin winch drives focal adhesion sliding and matrix assembly•Integrin switching mediates focal adhesion dynamics and fibronectin matrix assembly Lu et al. report that basement membranes can induce robust cellular fibronectin assembly using a contractile actomyosin winch, pulling on sliding focal adhesions to generate abundant fibronectin fibrils. This process involves integrin switching and can help to explain the widespread accumulation of fibronectin at many organ basement membranes.