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J. Biol. Chem., Vol. 281, Issue 5, 2901-2910, February 3, 2006

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

Yeh-Shiu Chu¹, Olivier Eder², William A. Thomas²³, Inbal Simcha^¶, Frederic Pincet^||, Avri Ben-Ze'ev^¶, Eric Perez^||, Jean Paul Thiery⁴, and Sylvie Dufour⁴⁵

From the UMR 144 CNRS-Institut Curie, 75248 Paris, France, the Department of Natural Sciences, Colby-Sawyer College, New London, New Hampshire 03257, the ^¶Department of Molecular Cell Biology, The Weizmann Institute of Science, 76100 Rehovot, Israel, and the ^||UMR 8550 CNRS-ENS, 75248 Paris, France

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 -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.

Received for publication, June 7, 2005 , and in revised form, October 3, 2005.

^* This work was supported by the Centre National de la Recherche Scientifique, the Institut Curie (Programme Incitatif et Coopératif, Physicochimie des Structures Biologiques Complexes), Association pour la Recherche sur le Cancer Grant 5653, European Economic Community Contract QLGI-CT-2001-00869, the Israel Cancer Research Foundation, the German-Israeli Foundation for Scientific Research and Development, and the Israel Science Foundation (to A. B.-Z.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.

¹ Supported by a France-Taiwan Ministry of Foreign Affairs Ph.D. fellowship.

² These authors contributed equally to this work.

³ Recipient of a Research and Development Award from Colby-Sawyer College.

⁴ Co-principal investigators.

⁵ To whom correspondence should be addressed. E-mail: Sylvie.Dufour{at}curie.fr.

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