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MBC in Press, published online ahead of print September 26, 2007
Mol. Biol. Cell 10.1091/mbc.E07-04-0378

A more recent version of this article appeared on December 1, 2007 Originally published as MBC in Press, 10.1091/mbc.E07-04-0378 on October 10, 2007
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Submitted on April 26, 2007
Revised on September 4, 2007
Accepted on September 14, 2007

CD44 and {beta}3 Integrin Organize Two Functionally Distinct Actin-based Domains in Osteoclasts

Anne Chabadel,* Inmaculada Bañon-Rodríguez,{dagger} David Cluet,* Bernhard Wehrle-Haller,{ddagger} Elisabeth Genot,{sect} Pierre Jurdic,* Ines M. Anton,{dagger} and Frédéric Saltel*{sect}

*Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Institut Fédératif Biosciences Gerland Lyon Sud, Université Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Ecole Normale Supérieure de Lyon, 69364 Lyon, France; {dagger}Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Cientificas-Universidad Autonoma de Madrid, 28049 Madrid, Spain; {ddagger}Department of Cellular Physiology and Metabolism, Centre Médical Universitaire, Geneva, Switzerland; {sect}European Institute of Chemistry and Biology, Unité Institut National de la Santé et de la Recherche Médicale 889, Université Victor Segalen Bordeaux 2, L’Institut Fédératif de Recherche 66, 33 600 Pessac, France

Monitoring Editor: David Drubin

The actin cytoskeleton of mature osteoclasts (OCs) adhering to nonmineralized substrates is organized in a belt of podosomes reminiscent of the sealing zone (SZ) found in bone resorbing OCs. In this study, we demonstrate that the belt is composed of two functionally different actin-based domains: podosome cores linked with CD44, which are involved in cell adhesion, and a diffuse cloud associated with {beta}3 integrin, which is involved in cell adhesion and contraction. WIP-/- OCs were devoid of podosomes, but still exhibited actin clouds. Indeed, WIP-/- OCs show diminished expression of WASp, which is required for podosome formation. CD44 is a novel marker of OC podosome cores and the first nonintegrin receptor detected in these structures. The importance of CD44 is revealed by showing that its clustering restores podosome cores and WASp expression in WIP-/- OCs. However, although CD44 signals are sufficient to form a SZ, the presence of WIP is indispensable for the formation of a fully functional SZ.

Address correspondence to: Pierre Jurdic (pjurdic{at}ens-lyon.fr)






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