CD44 and beta3 integrin organize two functionally distinct actin-based domains in osteoclasts.
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.
Chabadel
Anne
A
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Ecole Normale Supérieure de Lyon, 69364 Lyon, France.
Bañon-Rodríguez
Inmaculada
I
Cluet
David
D
Rudkin
Brian B
BB
Wehrle-Haller
Bernhard
B
Genot
Elisabeth
E
Jurdic
Pierre
P
Anton
Ines M
IM
Saltel
Frédéric
F
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001862:Bone Resorption; D018960:Hyaluronan Receptors / Q000378:metabolism*; D039661:Integrin beta3 / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000378:metabolism*; D015398:Signal Transduction; D051316:Wiskott-Aldrich Syndrome Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D000199:Actins; D018960:Hyaluronan Receptors; D039661:Integrin beta3; D051316:Wiskott-Aldrich Syndrome Protein