Gelsolin-Independent Podosome Formation in Dendritic Cells

Podosomes, important structures for adhesion and extracellular matrix degradation, are claimed to be involved in cell migration. In addition, podosomes are also reported to be of importance in tissue remodelling, e.g., in osteoclast-mediated bone resorption. Podosomes are highly dynamic actin-filament scaffolds onto which proteins important for their function, such as matrix metallo-proteases and integrins, attach. The dynamics of the podosomes require the action of many proteins regulating actin assembly and disassembly. One such protein, gelsolin, which associates to podosomes, has been reported to be important for podosome formation and function in osteoclasts. However, podosome-like structures have been reported in gelsolin-deficient dendritic cells, but the identity of these structures was not confirmed, and their dynamics and function was not investigated. Like many other cells, dendritic cells of the immune system also form matrix degrading podosomes. In the present study, we show that dendritic cells form podosomes independently of gelsolin, that there are no major alterations in their dynamics of formation and disassembly, and that they exhibit matrix-degrading function. Furthermore, we found that gelsolin is not required for TLR4-induced podosome disassembly. Thus, the actin cytoskeleton of podosomes involved in dendritic cell extracellular matrix degradation appears to be regulated differently than the cytoskeleton in podosomes of osteoclasts mediating bone resorption.足体（podosomes）是参与细胞黏附与细胞外基质降解的重要结构，被认为与细胞迁移密切相关。此外，足体在组织重塑过程中同样发挥关键作用，例如在破骨细胞介导的骨吸收过程中。足体属于高度动态的肌动蛋白丝支架，基质金属蛋白酶、整合素等对其功能至关重要的蛋白均可附着于此支架上。足体的动态特性依赖多种调控肌动蛋白组装与解聚的蛋白的协同作用。其中，凝溶胶蛋白（gelsolin）便是这类蛋白之一，已有研究表明其可招募至足体，对破骨细胞内足体的形成与功能具有重要意义。然而，有研究在凝溶胶蛋白缺陷型树突状细胞中观察到了类似足体的结构，但并未确认这些结构的本质，也未对其动态特性与功能开展研究。与诸多其他细胞类似，免疫来源的树突状细胞同样可形成具有基质降解能力的足体。本研究证实，树突状细胞可独立于凝溶胶蛋白形成足体，且其足体的组装与解聚动态未出现显著改变，同时仍具备基质降解功能。此外，我们还发现，凝溶胶蛋白并非Toll样受体4（TLR4）诱导的足体解聚过程所必需的蛋白。综上，参与树突状细胞细胞外基质降解的足体，其肌动蛋白细胞骨架的调控机制，与介导骨吸收的破骨细胞足体的调控机制存在显著差异。