寻找最薄弱的环节:探索整合素介导的机械分子途径。
Finding the weakest link: exploring integrin-mediated mechanical molecular pathways.
机构信息
University of Barcelona and Institute for Bioengineering of Catalonia, Barcelona, Spain.
出版信息
J Cell Sci. 2012 Jul 1;125(Pt 13):3025-38. doi: 10.1242/jcs.095794. Epub 2012 Jul 13.
From the extracellular matrix to the cytoskeleton, a network of molecular links connects cells to their environment. Molecules in this network transmit and detect mechanical forces, which subsequently determine cell behavior and fate. Here, we reconstruct the mechanical pathway followed by these forces. From matrix proteins to actin through integrins and adaptor proteins, we review how forces affect the lifetime of bonds and stretch or alter the conformation of proteins, and how these mechanical changes are converted into biochemical signals in mechanotransduction events. We evaluate which of the proteins in the network can participate in mechanotransduction and which are simply responsible for transmitting forces in a dynamic network. Besides their individual properties, we also analyze how the mechanical responses of a protein are determined by their serial connections from the matrix to actin, their parallel connections in integrin clusters and by the rate at which force is applied to them. All these define mechanical molecular pathways in cells, which are emerging as key regulators of cell function alongside better studied biochemical pathways.
从细胞外基质到细胞骨架,分子连接网络将细胞与其环境连接在一起。该网络中的分子传递和检测机械力,进而决定细胞的行为和命运。在这里,我们重建了这些力所遵循的机械途径。从基质蛋白到肌动蛋白,通过整合素和衔接蛋白,我们回顾了力如何影响键的寿命以及拉伸或改变蛋白质的构象,以及这些机械变化如何在机械转导事件中转化为生化信号。我们评估了网络中的哪些蛋白质可以参与机械转导,哪些蛋白质只是负责在动态网络中传递力。除了它们的个体特性外,我们还分析了蛋白质的机械响应如何由它们从基质到肌动蛋白的串联连接、整合素簇中的并联连接以及力施加到它们的速度决定。所有这些都定义了细胞中的机械分子途径,这些途径正在成为细胞功能的关键调节剂,与研究更为深入的生化途径并列。