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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 September 26, 2007
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Submitted on April 26, 2007
Revised on September 4, 2007
Accepted on September 14, 2007
3 Integrin Organize Two Functionally Distinct Actin-based Domains in Osteoclasts
*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, Unité Mixte de Recherche 5239 Centre National de la Recherche Scientifique/Ecole Normale Supérieur Lyon, Université Lyon 1, IFR 128 "BioSciences Lyon-Gerland," Ecole Normale Superieure de Lyon, 69364 Lyon Cedex 07, France;
Department of Cellular Physiology and Metabolism, CMU, Geneva, Switzerland; ||European Institute of Chemistry and Biology, Unité INSERM 889, Université Victor Segalen Bordeaux 2, IFR 66 2, 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
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.