E-cadherin junction formation involves an active kinetic nucleation process

Kabir H. Biswas, Kevin L. Hartman, Cheng Han Yu, Oliver J. Harrison, Hang Song, Adam W. Smith, William Y.C. Huang, Wan Chen Lin, Zhenhuan Guo, Anup Padmanabhan, Sergey M. Troyanovsky, Michael L. Dustin, Lawrence Shapiro, Barry Honig*, Ronen Zaidel-Bar, Jay T. Groves

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

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 (E-cad-ECD) 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.

Original languageEnglish
Pages (from-to)10932-10937
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number35
DOIs
StatePublished - 1 Sep 2015
Externally publishedYes

Keywords

  • Adhesion
  • Bilayer
  • Cadherin
  • Diffusion
  • Nucleation

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