Prototypical Type I E-cadherin and Type II Cadherin-7 Mediate Very Distinct Adhesiveness through Their Extracellular Domains

Yeh-Shiu Chu,Olivier Eder,William A Thomas,Inbal Simcha,Frederic Pincet,Avri Ben-Ze'Ev,Eric Perez,Jean Paul Thiery,Sylvie Dufour

doi:10.1074/jbc.m506185200

Abstract

Using a dual pipette assay that measures the force required to separate adherent cell doublets, we have quantitatively compared intercellular adhesiveness mediated by Type I (E- or N-cadherin) or Type II (cadherin-7 or -11) cadherins. At similar cadherin expression levels, cells expressing Type I cadherins adhered much more rapidly and strongly than cells expressing Type II cadherins. Using chimeric cadherins, we found that the extracellular domain exerts by far the dominant effect on cell adhesivity, that of E-cadherin conferring high adhesivity, and that of cadherin-7 conferring low adhesivity. Type I cadherins were incorporated to a greater extent into detergent-insoluble cytoskeletal complexes, and their cytoplasmic tails were much more effective in disrupting strong adherent junctions, suggesting that Type II cadherins form less stable complexes with beta-catenin. The present study demonstrates compellingly, for the first time, that cadherins are dramatically different in their ability to promote intercellular adhesiveness, a finding that has profound implications for the regulation of tissue morphogenesis.

Highlights

The pattern of cadherin expression during development is complex
E-cadherin, N-cadherin, and cadherin-7 co-precipitated at a comparable level with ␤- and ␣-catenin (Fig. 3). ␤-Catenin expression was used to estimate the cadherin content in Type I and Type II cadherin-expressing clones
We compare the adhesivity conferred upon cells by four different cadherins: E- and N-cadherin, and cadherin-7 and -11

Summary

Introduction

The pattern of cadherin expression during development is complex. For example, development of the neural crest involves epithelial to mesenchymal transitions, cell migration, cell aggregation, and cell differentiation [18], each of which is associated with tightly regulated, differential expression of Type I and II cadherins. Changes in the cadherins expressed on cells during morphogenesis and under pathological conditions are well documented [1,2,3]. Such differential expression would be even more effective if each cadherin promoted intercellular adhesion that is qualitatively or quantitatively unique. To test this possibility, we developed a dual pipette assay that quantifies precisely and reproducibly the force required to separate pairs of adherent cells [28, 29]. The results indicate that Type I cadherins (E and N) promote much stronger adhesiveness than Type II cadherins (7 and 11), the difference being attributable primarily to the extracellular domain of the molecules

Methods

Results

Conclusion