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Title: E-cadherin junction formation involves an active kinetic nucleation process

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [1];  [3];  [3];  [4];  [4];  [4];  [1];  [1];  [5];  [6];  [7];  [7];  [1];  [8]
  1. National Univ. of Singapore (Singapore)
  2. National Univ. of Singapore (Singapore); Univ. of California, Berkeley, CA (United States)
  3. Columiba Univ., New York, NY (United States)
  4. Univ. of California, Berkeley, CA (United States)
  5. Northwestern Univ., Chicago, IL (United States)
  6. Univ. of Oxford, Headington (United Kingdom)
  7. Columbia Univ., New York, NY (United States)
  8. National Univ. of Singapore (Singapore); Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab., Berkeley, CA (United States)

Epithelial (E)-cadherin-mediated cell–cell junctions play important roles in the development and maintenance of tissue structure in multicellular organisms. E-cadherin adhesion is thus a key element of the cellular microenvironment that provides both mechanical and biochemical signaling inputs. Here, we report in vitro reconstitution of junction-like structures between native E-cadherin in living cells and the extracellular domain of E-cadherin in a supported membrane. Junction formation in this hybrid live cell-supported membrane configuration requires both active processes within the living cell and a supported membrane with low E-cad-ECD mobility. The hybrid junctions recruit α-catenin and exhibit remodeled cortical actin. Observations suggest that the initial stages of junction formation in this hybrid system depend on the trans but not the cis interactions between E-cadherin molecules, and proceed via a nucleation process in which protrusion and retraction of filopodia play a key role.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-05CH11231; MCB-1412472; CRP001-084; NRF-RF2009-RF001-074; 100262/Z/12/Z; PRF #100262/Z/12/Z; R01 GM062270; AR44016
OSTI ID:
1221818
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, Issue 35; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 65 works
Citation information provided by
Web of Science

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Cited By (13)

Multicomponent Supported Membrane Microarray for Monitoring Spatially Resolved Cellular Signaling Reactions journal February 2018
Guiding hMSC Adhesion and Differentiation on Supported Lipid Bilayers journal November 2016
About Chemical Strategies to Fabricate Cell-Instructive Biointerfaces with Static and Dynamic Complexity journal May 2018
DNA mechanotechnology reveals that integrin receptors apply pN forces in podosomes on fluid substrates journal October 2019
Quantitative evaluation of the impact of artificial cell adhesion via DNA hybridization on E-cadherin-mediated cell adhesion journal March 2020
Platelet integrins exhibit anisotropic mechanosensing and harness piconewton forces to mediate platelet aggregation journal December 2017
Actin protrusions push at apical junctions to maintain E-cadherin adhesion journal December 2019
Binding equilibrium and kinetics of membrane-anchored receptors and ligands in cell adhesion: Insights from computational model systems and theory journal June 2016
How cells respond to environmental cues – insights from bio-functionalized substrates journal November 2016
Myosin-1c promotes E-cadherin tension and force-dependent recruitment of α-actinin to the epithelial cell junction journal May 2018
Cell–cell adhesion interface: orthogonal and parallel forces from contraction, protrusion, and retraction journal January 2018
Spatiomechanical Modulation of EphB4-Ephrin-B2 Signaling in Neural Stem Cell Differentiation journal September 2018
Correction: Corrigendum: Kinetic Measurements Reveal Enhanced Protein-Protein Interactions at Intercellular Junctions journal February 2017