CD44 and β3 Integrin Organize Two Functionally Distinct Actin-based Domains in Osteoclasts
Year: 2007
Type: article
Abstract: 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 beta3 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.
Source: Molecular Biology of the Cell
Institutions: Lyon 1 Université, École Normale Supérieure de Lyon, Centre National de la Recherche Scientifique, Institut de Génomique Fonctionnelle de Lyon, Institut National de la Recherche Agronomique, Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Laboratoire de Biologie et Modélisation de la Cellule, University of Geneva, Inserm, Institut Européen de Chimie et Biologie, Université Bordeaux Segalen
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: European Social Fund
OpenAlex ID: W2160358447