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JCS ePress
online publication date 2 Dec 2003
doi: 10.1242/jcs.00857
Research Article
Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways
Julie Gavard,
Mireille Lambert,
Inna Grosheva,
Véronique Marthiens,
Theano Irinopoulou,
Jean-François Riou,
Alexander Bershadsky,
and
René-Marc Mège*
* Author for correspondence (e-mail: mege{at}fer-a-moulin.inserm.fr)
Cell adhesion molecules of the cadherin family contribute to the regulation of cell shape and fate by mediating strong intercellular adhesion through Ca2+-dependent interaction of their ectodomain and association of their cytoplasmic tail to actin. However, the mechanisms co-ordinating cadherin-mediated adhesion with the reorganization of the actin cytoskeleton remain elusive. Here, the formation of de novo contacts was dissected by spreading cells on a highly active N-cadherin homophilic ligand. Cells responded to N-cadherin activation by extending lamellipodium and organizing cadherin-catenin complexes and actin filaments in cadherin adhesions. Lamellipodium protrusion, associated with actin polymerization at the leading edge sustained the extension of cadherin contacts through a phosphoinositide 3-kinase (PI 3-kinase)-Rac1 pathway. Cadherin adhesions were formed by PI 3-kinase-independent, Rac1-dependent co-recruitment of adhesion complexes and actin filaments. The expression and localization of p120 at the plasma membrane, associated with an increase in membrane-associated Rac1 was required for both cell responses, consistent with a major role of p120 in signalling pathways initiated by cadherin activation and contributing to Rac1-dependent contact extension and maturation. These results provide additional information on the mechanisms by which cadherin co-ordinates adhesion with dynamic changes in the cytoskeleton to control cell shape and intercellular junction organization.
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