β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments
β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments
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DOI：
10.1038/ncb2747
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发表时间：
2013-06-01
影响因子：
21.3
通讯作者：
Faessler, Reinhard
中科院分区：
文献类型：
--
作者：
Schiller, Herbert B.;Hermann, Michaela-Rosemarie;Faessler, Reinhard
结合同一类型细胞外基质蛋白的不同整合素如何介导特定功能尚不清楚。我们报道了β(1)-和α (v)-类整合素在纤维连接蛋白上的泛整合素缺失成纤维细胞中表达的功能分析。β(1)类整合素的重组促进了不依赖于肌球蛋白ii的小周围粘连和细胞突起的形成，而α (v)类整合素的表达诱导了大的局灶粘连的形成。这两类整合素的共同表达导致肌球蛋白完全激活和牵引力在坚硬的纤维连接蛋白覆盖的底物上发展，α (v)类整合素在暴露于高牵引力的粘附区域积累。定量蛋白质组学将α v类整合素与GEF-H1-RhoA途径联系在一起，该途径与formin mDia1结合，但与myosin II无关，α (5) β(1)整合素与RhoA-Rock-myosin II途径联系在一起。我们的研究为不同的纤维连接蛋白结合整合素分配了特定的功能，表明α (5) β(1)整合素完成了力的产生，而α (v)类整合素介导了对力的结构适应，这使得细胞能够感知基于纤维连接蛋白的微环境的刚性。
How different integrins that bind to the same type of extracellular matrix protein mediate specific functions is unclear. We report the functional analysis of beta(1)- and alpha(v)-class integrins expressed in pan-integrin-null fibroblasts seeded on fibronectin. Reconstitution with beta(1)-class integrins promotes myosin-II-independent formation of small peripheral adhesions and cell protrusions, whereas expression of alpha(v)-class integrins induces the formation of large focal adhesions. Co-expression of both integrin classes leads to full myosin activation and traction-force development on stiff fibronectin-coated substrates, with alpha(v)-class integrins accumulating in adhesion areas exposed to high traction forces. Quantitative proteomics linked alpha v-class integrins to a GEF-H1-RhoA pathway coupled to the formin mDia1 but not myosin II, and alpha(5)beta(1) integrins to a RhoA-Rock-myosin II pathway. Our study assigns specific functions to distinct fibronectin-binding integrins, demonstrating that alpha(5)beta(1) integrins accomplish force generation, whereas alpha(v)-class integrins mediate the structural adaptations to forces, which cooperatively enable cells to sense the rigidity of fibronectin-based microenvironments.