Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 10, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2019845118
Keywords
cadherin; cell adhesion; adherens junctions; single-molecule tracking; FRET
Categories
Funding
- National Institute of General Medical Sciences of the NIH [1R01GM117104]
- HHMI
Ask authors/readers for more resources
Cadherin transmembrane proteins play important roles in intercellular adhesion and tissue morphogenesis. Experimental evidence shows mutual cooperativity between lateral cis and adhesive trans interactions, leading to the assembly of large intermembrane junctions. This cooperativity is primarily due to allostery and provides insights into how weak cis and trans interactions work together to create strong cell adhesions.
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 Forster 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available