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DOI10.1073/pnas.2019845118
Cadherin cis and trans interactions are mutually cooperative
Thompson C.J.; Vu V.H.; Leckband D.E.; Schwartz D.K.
发表日期2021
ISSN00278424
卷号118期号:10
英文摘要Cadherin transmembrane proteins are responsible for intercellular adhesion in all biological tissues and modulate tissue morphogenesis, cell motility, force transduction, and macromolecular transport. The protein-mediated adhesions consist of adhesive trans interactions and lateral cis interactions. Although theory suggests cooperativity between cis and trans bonds, direct experimental evidence of such cooperativity has not been demonstrated. Here, the use of superresolution microscopy, in conjunction with intermolecular single-molecule Förster resonance energy transfer, demonstrated the mutual cooperativity of cis and trans interactions. Results further demonstrate the consequent assembly of large intermembrane junctions, using a biomimetic lipid bilayer cell adhesion model. Notably, the presence of cis interactions resulted in a nearly 30-fold increase in trans-binding lifetimes between epithelial-cadherin extracellular domains. In turn, the presence of trans interactions increased the lifetime of cis bonds. Importantly, comparison of trans-binding lifetimes of small and large cadherin clusters suggests that this cooperativity is primarily due to allostery. The direct quantitative demonstration of strong mutual cooperativity between cis and trans interactions at intermembrane adhesions provides insights into the long-standing controversy of how weak cis and trans interactions act in concert to create strong macroscopic cell adhesions. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Adherens junctions; Cadherin; Cell adhesion; FRET; Single-molecule tracking
语种英语
scopus关键词cadherin; adherens junction; allosterism; Article; binding affinity; biomimetics; cell adhesion; cell junction; controlled study; diffusion; embryo; fluorescence resonance energy transfer; human; human cell; lipid bilayer; microscopy; priority journal; protein interaction
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180347
作者单位Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, United States; Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, United States; Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, United States
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Thompson C.J.,Vu V.H.,Leckband D.E.,et al. Cadherin cis and trans interactions are mutually cooperative[J],2021,118(10).
APA Thompson C.J.,Vu V.H.,Leckband D.E.,&Schwartz D.K..(2021).Cadherin cis and trans interactions are mutually cooperative.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA Thompson C.J.,et al."Cadherin cis and trans interactions are mutually cooperative".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).
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