期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 47, 页码 18331-18336出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0806783105
关键词
cancer; cell adhesion; single-molecule force spectroscopy; actin
资金
- American Heart Association [0855319E]
- FCT Portugal [PTDC/SAU-OBD/64319/2006]
- National Institutes of Health [GM080673]
- Johns Hopkins Institute for NanoBioTechnology
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-OBD/64319/2006] Funding Source: FCT
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据