Involvement of actin polymerization in podosome dynamics
Involvement of actin polymerization in podosome dynamics
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DOI：
10.1242/jcs.075903
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发表时间：
2012-04-01
影响因子：
4
通讯作者：
Geiger, Benjamin
中科院分区：
文献类型：
--
作者：
Luxenburg, Chen;Winograd-Katz, Sabina;Geiger, Benjamin
足小体由不同的单核细胞衍生物形成，是一种小的粘附结构，其协调动力学和细胞骨架重组驱动其运动性和侵袭性特征。利用活细胞显微镜，我们探索了培养破骨细胞中足小体从头组装和拆卸的时间分子步骤。我们在此证明，足小体组装中最早可见的步骤是斑块蛋白paxillin的局部积累，以及稳定肌动蛋白网络的接触层，随后是肌动蛋白细丝的强大聚合及其与α -肌动蛋白的结合。只有在这个时候，在足多体环区域，整合素β 3水平的局部增加才会很明显。因此，在接触蛋白和paxillin富集部位的局部肌动蛋白聚合在β 3整合素的局部积累之前使足质体组装成核。我们进一步表明，肌动蛋白聚合对于成熟的足多体环结构域中斑块蛋白的募集和维持也很重要。我们的模型表明，核心束动力学在调节足体稳定性方面起着核心作用。
Podosomes, which are formed by different monocyte derivatives, are small adhesion structures whose coordinated dynamics and cytoskeletal reorganization drive their motile and invasive features. Using live-cell microscopy, we explored the temporal molecular steps of the de novo assembly and disassembly of podosomes in cultured osteoclasts. We demonstrate here that the earliest visible step in podosome assembly is the local accumulation of the plaque protein paxillin, along with cortactin, which stabilizes actin networks, followed by robust polymerization of actin filaments and their association with alpha-actinin. Only then is a local increase in integrin beta 3 levels apparent in the podosome ring domain. Thus, local actin polymerization in cortactin-and paxillin-rich locations nucleates podosome assembly before the local accumulation of beta 3 integrin. We further show that actin polymerization is also important for the recruitment and maintenance of plaque proteins in the mature podosome ring domain. Our model implies that core bundle dynamics play a central role in regulating podosome stability.