Departments of Chemical and Biomolecular Engineering, Chemistry, and Biochemistry, University of Illinois, Urbana, Illinois 61801; email:
Annu Rev Cell Dev Biol. 2014;30:291-315. doi: 10.1146/annurev-cellbio-100913-013212. Epub 2014 Jul 9.
Cadherins are the principal adhesion proteins at intercellular junctions and function as the biochemical Velcro that binds cells together. Besides this mechanical function, cadherin complexes are also mechanotransducers that sense changes in tension and trigger adaptive reinforcement of intercellular junctions. The assembly and regulation of cadherin adhesions are central to their mechanical functions, and new evidence is presented for a comprehensive model of cadherin adhesion, which is surprisingly more complex than previously appreciated. Recent findings also shed new light on mechanisms that regulate cadherin junction assembly, adhesion, and mechanotransduction. We further describe recent evidence for cadherin-based mechanotransduction, and the rudiments of the molecular mechanism, which involves α-catenin and vinculin as key elements. Potential roles of a broader cast of possible force-sensitive partners are considered, as well as known and speculative biological consequences of adhesion and force transduction at cadherin-mediated junctions.
钙黏蛋白是细胞间连接的主要黏附蛋白,作为生物化学的维可牢,将细胞结合在一起。除了这种机械功能外,钙黏蛋白复合物也是机械感受器,能够感知张力的变化,并触发细胞间连接的适应性增强。钙黏附蛋白黏附的组装和调节是其机械功能的核心,目前提出了一个全面的钙黏附蛋白黏附模型,该模型比以前认为的要复杂得多。最近的发现也为调节钙黏蛋白连接组装、黏附和机械转导的机制提供了新的线索。我们进一步描述了基于钙黏蛋白的机械转导的最新证据,以及分子机制的基本原理,其中涉及α-连环蛋白和纽蛋白作为关键元件。还考虑了更广泛的可能力敏伙伴的潜在作用,以及钙黏蛋白介导的连接中黏附和力转导的已知和推测的生物学后果。