Luxenburg Chen, Addadi Lia, Geiger Benjamin
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Eur J Cell Biol. 2006 Apr;85(3-4):203-11. doi: 10.1016/j.ejcb.2005.11.002. Epub 2005 Dec 19.
Podosomes are 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 on published data and on 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 sealing 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.
足体是在骨吸收中起核心作用的特殊黏附结构。在本文中，我们探讨了足体在不同组织状态下的分子多样性和动态变化，其范围从在非极化细胞的整个腹侧膜上的分散分布，到足体簇的形成、发育成环，再到外周带的组装，类似于极化的骨吸收破骨细胞的封闭区。基于已发表的数据和我们自己的研究结果，我们在此描述了关键的足体相关蛋白之间的空间关系。通过定量显微镜观察，我们发现当簇状足体转变为环和类似封闭区的结构时，F-肌动蛋白、纽蛋白、桩蛋白和α-辅肌动蛋白的局部水平会急剧增加。这种变化伴随着同一区域磷酸酪氨酸水平的显著下降。因此，我们的数据表明，在破骨细胞极化过程中，足体的分子组成发生了重大变化，这种变化可能与黏附“增强”有关，而黏附“增强”与骨吸收装置的组装相关。研究经历去磷酸化的蛋白质的性质对于理解调节上述过程的机制至关重要。
