School of Medicine, Shandong University, Jinan, Shandong 250012, China; Cell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA; Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Gastroenterology, Qilu Hospital, Jinan, Shandong 250012, China.
Cell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Dev Cell. 2020 Mar 9;52(5):631-646.e4. doi: 10.1016/j.devcel.2020.01.007. Epub 2020 Jan 30.
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.
我们发现基底膜及其主要成分可以诱导快速、显著的纤维连接蛋白组织。在这个新的基质组装机制中，基于α5β1 整联蛋白的粘着斑通过肌球蛋白 IIA 相关的肌动蛋白应力纤维的动态缩短，主动向细胞腹侧中心滑动，从而驱动远离粘着点的快速纤维连接蛋白纤维原纤维的形成。这种机制与基于稳定或固定位置粘着斑的经典纤维连接蛋白组装形成鲜明对比，后者包含αVβ3 整联蛋白和α5β1 整联蛋白向近端纤维状粘着斑的易位。在基底膜成分上，这些滑动粘着斑包含标准粘着斑成分，但完全缺乏经典的αVβ3 整联蛋白。相反，周围的α3β1 或α2β1 粘着斑介导初始细胞附着，但随着时间的推移，它们会转变为基于α5β1 整联蛋白的滑动粘着斑，以组装纤维连接蛋白基质。这种基底膜触发的机制产生了快速的纤维连接蛋白纤维原纤维形成，为广泛存在于许多器官基底膜中的纤维连接蛋白的广泛积累提供了一种机制解释。
