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Vol. 18, Issue 12, 4899-4910, December 2007

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CD44 and β3 Integrin Organize Two Functionally Distinct Actin-based Domains in Osteoclasts

Anne Chabadel^*, Inmaculada Bañon-Rodríguez, David Cluet, Brian B. Rudkin, Bernhard Wehrle-Haller, Elisabeth Genot^||, Pierre Jurdic^*, Ines M. Anton, and Frédéric Saltel^*,||

*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; Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Cientificas-Universidad Autonoma de Madrid, 28049 Madrid, Spain; Laboratoire de Biologie Moléculaire de la Cellule, Unite Mixte de Recherche 5239 Centre National de la Recherche Scientifique/Ecole Normale Supérieure Lyon, Université Lyon I, Institut Fédératif de Recherche "BioSciences Lyon-Gerland," Ecole Normale Superieure de Lyon, 69364 Lyon Cedex 07, France; Department of Cellular Physiology and Metabolism, Centre Médical Universitaire, 1211 Geneva 4, Switzerland; and ^||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

Submitted April 26, 2007; Revised September 4, 2007; Accepted September 14, 2007
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 β3 integrin, which is involved in cell adhesion and contraction. Wiskott Aldrich Syndrome Protein (WASp) Interacting Protein (WIP)–/– OCs were devoid of podosomes, but they 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).