The molecular dynamics of osteoclast adhesions

Podosomes Lire specialized adhesive Structures that play a central role in bone resorption. In this article we address the molecular diversity and dynamics of podosomes at different states of organization, ranging from scattered distribution over the entire ventral membrane of non-polarized cells, via formation of podosome clusters and developing rings to the assembly of a peripheral belt, resembling the sealing zone of polarized, bone-resorbing osteoclasts. Based oil published data and Oil Our own results, we describe here the spatial relationships between key podosome-associated proteins. Using quantitative microscopy, we show here a dramatic increase in the local levels of F-actin, vinculin, paxillin, and alpha-actinin, which occurs upon the transformation of clustered podosomes into rings and scaling zone-like structures. This change is accompanied by a marked decrease in phosphotyrosine levels in the same region. Therefore. Our data suggest that a major change in the molecular composition of podosomes is taking place during osteoclast polarization, a change that may be related to adhesion reinforcement, associated with the assembly of the bone-resorbing apparatus. Studying the nature of the proteins that undergo de-phosphorylation is critical For the understanding of the mechanisms regulating the processes described above. (c) 2005 Elsevier GmbH. All rights reserved.