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破骨细胞中的Rho GTP酶:足体排列的协调者

Rho GTPases in osteoclasts: orchestrators of podosome arrangement.

作者信息

Ory Stéphane, Brazier Hélène, Pawlak Géraldine, Blangy Anne

机构信息

Centre de Recherche de Biochimie Macromoléculaire, UM2, CNRS, Montpellier, France.

出版信息

Eur J Cell Biol. 2008 Sep;87(8-9):469-77. doi: 10.1016/j.ejcb.2008.03.002. Epub 2008 Apr 23.

DOI:10.1016/j.ejcb.2008.03.002
PMID:18436334
Abstract

Cells from the myeloid lineage, namely macrophages, dendritic cells and osteoclasts, develop podosomes instead of stress fibers and focal adhesions to adhere and migrate. Podosomes share many components with focal adhesions but differ in their molecular organization, with a dense core of polymerized actin surrounded by scaffolding proteins, kinases and integrins. Podosomes are found either isolated both in macrophages and dendritic cells or arranged into superstructures in osteoclasts. When osteoclasts resorb bone, they form an F-actin rich sealing zone, which is a dense array of connected podosomes that firmly anchors osteoclasts to bone. It delineates a compartment in which protons and proteases are secreted to dissolve and degrade the mineralized matrix. Since Rho GTPases have been shown to control F-actin stress fibers and focal adhesions in mesenchymal cells, the question of whether they could also control podosome formation and arrangement in cells from the myeloid lineage, and particularly in osteoclasts, rapidly emerged. This article considers recent advances made in our understanding of podosome arrangements in osteoclasts and how Rho GTPases may control it.

摘要

髓系细胞谱系中的细胞,即巨噬细胞、树突状细胞和破骨细胞,会形成足体而非应力纤维和黏着斑来实现黏附和迁移。足体与黏着斑有许多共同成分,但分子组织方式不同,其由聚合肌动蛋白的致密核心以及周围的支架蛋白、激酶和整合素组成。足体在巨噬细胞和树突状细胞中呈孤立状态,而在破骨细胞中则排列成超结构。当破骨细胞吸收骨质时,它们会形成富含丝状肌动蛋白(F-肌动蛋白)的封闭带,这是由相连足体组成的致密阵列,能将破骨细胞牢固地锚定在骨头上。它划定了一个隔室,质子和蛋白酶在其中分泌,以溶解和降解矿化基质。由于Rho鸟苷三磷酸酶(Rho GTPases)已被证明可控制间充质细胞中的F-肌动蛋白应力纤维和黏着斑,于是一个问题迅速浮现:它们是否也能控制髓系细胞谱系中的细胞,尤其是破骨细胞中的足体形成和排列。本文探讨了我们在理解破骨细胞中足体排列以及Rho GTPases如何对其进行控制方面取得的最新进展。

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