Mui Keeley L, Chen Christopher S, Assoian Richard K
Department of Systems Pharmacology and Translational Therapeutics, Program in Translational Biomechanics, Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
J Cell Sci. 2016 Mar 15;129(6):1093-100. doi: 10.1242/jcs.183699. Epub 2016 Feb 26.
Cadherins and integrins are intrinsically linked through the actin cytoskeleton and share common signaling molecules. Although mechanosensing by the integrin-actin axis has long been appreciated, a growing body of literature now demonstrates that cadherins also transduce and respond to mechanical forces. Mounting evidence shows that mechanically driven crosstalk between integrins and cadherins regulates the spatial distribution of these receptors, their signaling intermediates, the actin cytoskeleton and intracellular forces. This interplay between integrins and cadherins can control fibronectin matrix assembly and signaling, and a fine balance between traction forces at focal adhesions and intercellular tension at adherens junctions is crucial for directional collective cell migration. In this Commentary, we discuss two central ideas: (1) how the dynamic interplay between integrins and cadherins regulates the spatial organization of intracellular signals and the extracellular matrix, and (2) the emerging consensus that intracellular force is a central mechanism that dictates cell behavior, guides tissue development and ultimately drives physiology.
钙黏蛋白和整合素通过肌动蛋白细胞骨架内在地联系在一起，并共享共同的信号分子。尽管整合素-肌动蛋白轴的机械传感作用早已为人所知，但现在越来越多的文献表明，钙黏蛋白也能转导并响应机械力。越来越多的证据表明，整合素和钙黏蛋白之间由机械力驱动的相互作用调节着这些受体、它们的信号中间体、肌动蛋白细胞骨架和细胞内力的空间分布。整合素和钙黏蛋白之间的这种相互作用可以控制纤连蛋白基质的组装和信号传导，而粘着斑处的牵引力和黏着连接处的细胞间张力之间的精细平衡对于定向集体细胞迁移至关重要。在本述评中，我们讨论两个核心观点：（1）整合素和钙黏蛋白之间的动态相互作用如何调节细胞内信号和细胞外基质的空间组织，以及（2）新出现的共识，即细胞内力是决定细胞行为、指导组织发育并最终驱动生理功能的核心机制。
