Podosome and sealing zone: Specificity of the osteoclast model
Podosome and sealing zone: Specificity of the osteoclast model
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DOI：
10.1016/j.ejcb.2005.09.008
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发表时间：
2006-04-01
影响因子：
6.6
通讯作者：
Destaing, O
中科院分区：
文献类型：
--
作者：
Jurdic, P;Saltel, F;Destaing, O
破骨细胞的骨吸收功能依赖于肌动蛋白细胞骨架的完整性。根据破骨细胞散布的基质不同，肌动蛋白有两种不同的结构，称为足小体和封闭区。为了了解足小体与封闭区之间的特殊性质和关系，我们对培养的破骨细胞进行了活细胞成像。当在细胞外基质成分上培养时，这些细胞中的足质体组织成高阶结构。在完全分化的细胞中，这些聚集的足小体稍后会排列成动态的短寿命环，最终扩展到细胞周围，形成稳定的长寿命足小体带。在破骨细胞中，这种特定的足体模式是由微管（MTs）控制的。事实上，诺可达唑治疗不影响足体的形成，而只影响簇/环和带之间的过渡。在这一转变过程中，mt通过乙酰化积累了微管蛋白的特定翻译后修饰。这一过程受到GTPase Rho、其效应物mDIA2和最近发现的微管蛋白去乙酰化酶HDAC6的抑制途径的抑制。这种乙酰化的具体功能尚不清楚，但在活性破骨细胞中也观察到形成封闭区，这也是依赖于NIT的。因此，足状体带似乎与封闭带相似。实际上，足体带和密封带的特点是整体稳定。尽管它们的行为相似，但封闭区不是由足质体融合形成的。足体带或封闭带的形成受外部环境控制。事实上，只有骨矿物部分，即磷灰石晶体，能够在成熟的破骨细胞中诱导封闭区形成。破骨细胞与磷灰石接触刺激非受体酪氨酸激酶c-Sre和GTPase Rho以形成封闭区。正如我们将在这篇综述中讨论的那样，足质体和封闭带似乎有着惊人的联系。(c) 2005 Elsevier GmbH版权所有。
The bone resorption function of osteoclasts is dependent on the integrity of the actin cytoskeleton. Depending on the substratum upon which the osteoclasts are spread, there are two different structures of actin known as podosomes and the sealing zone. To understand the specific properties and relationship of podosomes and the sealing zone, we used live-cell imaging of cultured osteoclasts. When cultured on extracellular matrix components, podosomes in these cells are organized in higher-ordered structures. These are clustered podosomes that will arrange later into dynamic short-lived rings which finally expand to the cell periphery to form a stable long-lived podosome belt in fully differentiated cells. In osteoclasts, this specific podosome patterning is under the control of microtubules (MTs). Indeed, nocodazole treatment does not affect podosome formation but only the transition between clusters/rings and belts. During this transition, MTs accumulate a specific post-translational modification of tubulin by acetylation. This process is repressed by an inhibitory pathway involving the GTPase Rho, its effector mDIA2 and the recently discovered tubulin deacetylase HDAC6. The specific function of this acetylation is still unknown but is also observed in active osteoclasts forming a sealing zone which is also NIT dependent. Thus, it appears that the podosome belt is reminiscent of the sealing zone. Indeed, podosome belts and sealing zones are characterized by their overall stability. Despite their similar behavior, a sealing zone is not formed by fusion of podosomes. The formation of a podosome belt or a sealing zone is controlled by the external environment. Indeed, only the bone mineral fraction, known as apatite crystal, is able to induce sealing zone formation in mature osteoclasts. Contact of osteoclasts with apatite stimulates the non-receptor tyrosine kinase c-Sre and the GTPase Rho in order to form the sealing zone. As we will discuss in this review, it appears that podosomes and the sealing zone are strikingly linked. (c) 2005 Elsevier GmbH. All rights reserved.