CD44 and β3 integrin organize two functionally distinct actin-based domains in osteoclasts
CD44 and β3 integrin organize two functionally distinct actin-based domains in osteoclasts
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DOI：
10.1091/mbc.e07-04-0378
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发表时间：
2007-12-01
影响因子：
3.3
通讯作者：
Saltel, Frederic
中科院分区：
文献类型：
--
作者：
Chabadel, Anne;Banon-Rodriguez, Inmaculada;Saltel, Frederic
肌动蛋白细胞骨架的成熟破骨细胞（OC）坚持非矿化基板组织在一条带的podosomes让人想起骨吸收OC中发现的密封区（SZ）。在这项研究中，我们表明，带是由两个功能不同的肌动蛋白为基础的域：与CD 44，这是参与细胞粘附，和弥漫性云与133整合素，这是参与细胞粘附和收缩的连接的足状体核心。Wiskott Aldrich综合征蛋白（WASp）相互作用蛋白（WASp）-/-OC缺乏podosomes，但它们仍显示肌动蛋白云。事实上，β-/-OC显示出减少的WASp表达，这是足体形成所需的。CD 44是OC足状体核心的新标记物，并且是在这些结构中检测到的第一个非整合素受体。CD 44的重要性通过显示其聚集恢复了β-/-OC中的足体核心和WASp表达来揭示。然而，尽管CD 44信号足以形成SZ，但CD 44的存在对于形成全功能SZ是必不可少的。
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 133 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.