Bajpai Saumendra, Correia Joana, Feng Yunfeng, Figueiredo Joana, Sun Sean X, Longmore Gregory D, Suriano Gianpaolo, Wirtz Denis
Department of Chemical and Biomolecular Engineering, and Howard Hughes Medical Institute Graduate Training Program and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18331-6. doi: 10.1073/pnas.0806783105. Epub 2008 Nov 18.
alpha-Catenin is essential in cadherin-mediated epithelium development and maintenance of tissues and in cancer progression and metastasis. However, recent studies question the conventional wisdom that alpha-catenin directly bridges the cadherin adhesion complex to the actin cytoskeleton. Therefore, whether alpha-catenin plays a direct role in cadherin-dependent cell adhesion is unknown. Here, single-molecule force spectroscopy measurements in cells depleted of alpha-catenin or expressing the hereditary diffuse gastric cancer associated V832M E-cadherin germ-line missense mutation show that alpha-catenin plays a critical role in cadherin-mediated intercellular recognition and subsequent multibond formation within the first 300 ms of cell contact. At short contact times, alpha-catenin mediates a 30% stronger interaction between apposing E-cadherin molecules than when it cannot bind the E-cadherin-beta-catenin complex. As contact time between cells increases, alpha-catenin is essential for the strengthening of the first intercellular cadherin bond and for the ensuing formation of additional bonds between the cells, all without the intervention of actin. These results suggest that a critical decision to form an adhesion complex between 2 cells occurs within an extremely short time span and at a single-molecule level and identify a previously unappreciated role for alpha-catenin in these processes.
α-连环蛋白在钙黏蛋白介导的上皮组织发育、组织维持以及癌症进展和转移过程中至关重要。然而，最近的研究对α-连环蛋白直接将钙黏蛋白黏附复合体与肌动蛋白细胞骨架相连的传统观点提出了质疑。因此，α-连环蛋白是否在钙黏蛋白依赖性细胞黏附中发挥直接作用尚不清楚。在此，对缺乏α-连环蛋白或表达与遗传性弥漫性胃癌相关的V832M E-钙黏蛋白种系错义突变的细胞进行单分子力谱测量表明，α-连环蛋白在细胞接触的最初300毫秒内，在钙黏蛋白介导的细胞间识别以及随后的多键形成过程中发挥着关键作用。在短接触时间内，与无法结合E-钙黏蛋白-β-连环蛋白复合体时相比，α-连环蛋白介导相对的E-钙黏蛋白分子之间的相互作用强30%。随着细胞间接触时间的增加，α-连环蛋白对于加强第一个细胞间钙黏蛋白键以及随后细胞间形成额外的键至关重要，所有这些过程均无需肌动蛋白的干预。这些结果表明，两个细胞之间形成黏附复合体的关键决定在极短的时间跨度内且在单分子水平上发生，并确定了α-连环蛋白在这些过程中一个先前未被认识到的作用。
