Cadherin interactions ensure the correct registry and anchorage of cells during tissue formation. Along the plasma membrane, cadherins form inter-junctional lattices via cis- and trans-dimerization. While structural studies have provided models for cadherin interactions, the molecular nature of cadherin binding in vivo remains unexplored. We undertook a multi-disciplinary approach combining live cell imaging of three-dimensional cell assemblies (spheroids) with a computational model to study the dynamics of N-cadherin interactions. Using a loss-of-function strategy, we demonstrate that each N-cadherin interface plays a distinct role in spheroid formation. We found that cis-dimerization is not a prerequisite for trans-interactions, but rather modulates trans-interfaces to ensure tissue stability. Using a model of N-cadherin junction dynamics, we show that the absence of cis-interactions results in low junction stability and loss of tissue integrity. By quantifying the binding and unbinding dynamics of the N-cadherin binding interfaces, we determined that mutating either interface results in a 10-fold increase in the dissociation constant. These findings provide new quantitative information on the steps driving cadherin intercellular adhesion and demonstrate the role of cis-interactions in junction stability.
Description
Lateral assembly of N-cadherin drives tissue integrity by stabilizing adherens junctions | Journal of The Royal Society Interface
%0 Journal Article
%1 Garg20141055
%A Garg, S.
%A Fischer, S. C.
%A Schuman, E. M.
%A Stelzer, E. H. K.
%D 2015
%I The Royal Society
%J Journal of The Royal Society Interface
%K csi sabinefischer
%P 20141055
%R 10.1098/rsif.2014.1055
%T Lateral assembly of N-cadherin drives tissue integrity by stabilizing adherens junctions
%U http://rsif.royalsocietypublishing.org/content/12/104/20141055
%V 12
%X Cadherin interactions ensure the correct registry and anchorage of cells during tissue formation. Along the plasma membrane, cadherins form inter-junctional lattices via cis- and trans-dimerization. While structural studies have provided models for cadherin interactions, the molecular nature of cadherin binding in vivo remains unexplored. We undertook a multi-disciplinary approach combining live cell imaging of three-dimensional cell assemblies (spheroids) with a computational model to study the dynamics of N-cadherin interactions. Using a loss-of-function strategy, we demonstrate that each N-cadherin interface plays a distinct role in spheroid formation. We found that cis-dimerization is not a prerequisite for trans-interactions, but rather modulates trans-interfaces to ensure tissue stability. Using a model of N-cadherin junction dynamics, we show that the absence of cis-interactions results in low junction stability and loss of tissue integrity. By quantifying the binding and unbinding dynamics of the N-cadherin binding interfaces, we determined that mutating either interface results in a 10-fold increase in the dissociation constant. These findings provide new quantitative information on the steps driving cadherin intercellular adhesion and demonstrate the role of cis-interactions in junction stability.
@article{Garg20141055,
abstract = {Cadherin interactions ensure the correct registry and anchorage of cells during tissue formation. Along the plasma membrane, cadherins form inter-junctional lattices via cis- and trans-dimerization. While structural studies have provided models for cadherin interactions, the molecular nature of cadherin binding in vivo remains unexplored. We undertook a multi-disciplinary approach combining live cell imaging of three-dimensional cell assemblies (spheroids) with a computational model to study the dynamics of N-cadherin interactions. Using a loss-of-function strategy, we demonstrate that each N-cadherin interface plays a distinct role in spheroid formation. We found that cis-dimerization is not a prerequisite for trans-interactions, but rather modulates trans-interfaces to ensure tissue stability. Using a model of N-cadherin junction dynamics, we show that the absence of cis-interactions results in low junction stability and loss of tissue integrity. By quantifying the binding and unbinding dynamics of the N-cadherin binding interfaces, we determined that mutating either interface results in a 10-fold increase in the dissociation constant. These findings provide new quantitative information on the steps driving cadherin intercellular adhesion and demonstrate the role of cis-interactions in junction stability.},
added-at = {2018-10-02T15:42:23.000+0200},
author = {Garg, S. and Fischer, S. C. and Schuman, E. M. and Stelzer, E. H. K.},
biburl = {https://www.bibsonomy.org/bibtex/240a3402ac140ac526ef4bd3e7a252d3f/scfischer},
description = {Lateral assembly of N-cadherin drives tissue integrity by stabilizing adherens junctions | Journal of The Royal Society Interface},
doi = {10.1098/rsif.2014.1055},
eprint = {http://rsif.royalsocietypublishing.org/content/12/104/20141055.full.pdf},
interhash = {b771f6bfc867c6a66e3e5e6c23635c45},
intrahash = {40a3402ac140ac526ef4bd3e7a252d3f},
issn = {1742-5689},
journal = {Journal of The Royal Society Interface},
keywords = {csi sabinefischer},
pages = 20141055,
publisher = {The Royal Society},
timestamp = {2019-01-15T08:46:11.000+0100},
title = {Lateral assembly of N-cadherin drives tissue integrity by stabilizing adherens junctions},
url = {http://rsif.royalsocietypublishing.org/content/12/104/20141055},
volume = 12,
year = 2015
}