title: There are four dynamically and functionally distinct populations of E-cadherin in cell junctions.
abstract: E-cadherin is a trans-membrane tumor suppressor responsible for epithelial cell adhesion. E-cadherin forms adhesive clusters through combined extra-cellular cis- and trans-interactions and intracellular interaction with the actin cytoskeleton. Here we identify four populations of E-cadherin within cell junctions based on the molecular interactions which determine their mobility and adhesive properties. Adhesive and non-adhesive populations of E-cadherin each consist of mobile and immobile fractions. Up to half of the E-cadherin immobilized in cell junctions is non-adhesive. Incorporation of E-cadherin into functional adhesions require all three adhesive interactions, with deletion of any one resulting in loss of effective cell-cell adhesion. Interestingly, the only interaction which could independently slow the diffusion of E-cadherin was the tail-mediated intra-cellular interaction. The adhesive and non-adhesive mobile fractions of E-cadherin can be distinguished by their sensitivity to chemical cross-linking with adhesive clusters. Our data define the size, mobility, and adhesive properties of four distinct populations of E-cadherin within cell junctions, and support association with the actin cytoskeleton as the first step in adhesion formation.
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow G11 7DU, UK.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Erami
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow G11 7DU, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Timpson
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Wu
authors.initials: W
authors.lastname: Yao
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Ronen
authors.initials: R
authors.lastname: Zaidel-Bar
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow G11 7DU, UK k.anderson@beatson.gla.ac.uk.
authors.forename: Kurt I
authors.initials: KI
authors.lastname: Anderson
keywords: Cell adhesion; E-cadherin; FRAP; Super-resolution microscopy