Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
Sci Rep. 2018 Jan 11;8(1):524. doi: 10.1038/s41598-017-18861-2.
Podosomes are dynamic actin-based membrane protrusions that are important for extracellular matrix degradation and invasive cell motility. Individual podosomes are often found to organize into large rosette-like structures in some types of cells, such as osteoclasts, endothelial cells, Src-transformed fibroblasts, and certain highly invasive cancer cells. In this study, we show that new podosome rosettes arise through one of two mechanisms; de novo assembly or fission of a pre-existing podosome rosette in Src-transformed fibroblasts. Fission is a more efficient way than de novo assembly to generate new podosome rosettes in these cells. Podosome rosettes undergoing fission possess higher motility and a stronger matrix-degrading capability. Podosome rosette fission may be the result of polarized myosin II-mediated contractility of these structures, which is coordinately regulated by myosin light chain kinase and Rho-associated kinase II. Collectively, this study unveils a previously unknown mechanism-fission for the biogenesis of podosome rosettes.
足突是一种基于肌动蛋白的动态细胞膜突起，对于细胞外基质的降解和细胞的侵袭性运动非常重要。在某些类型的细胞中，如破骨细胞、内皮细胞、Src 转化的成纤维细胞和某些高侵袭性癌细胞，单个足突经常被发现组织成大型玫瑰花结样结构。在这项研究中，我们表明，Src 转化的成纤维细胞中新的足突玫瑰花结的形成有两种机制之一：从头组装或预先存在的足突玫瑰花结的分裂。在这些细胞中，分裂是比从头组装更有效地产生新的足突玫瑰花结的方式。正在发生分裂的足突玫瑰花结具有更高的迁移性和更强的基质降解能力。足突玫瑰花结的分裂可能是这些结构的极化肌球蛋白 II 介导的收缩的结果，这种收缩受到肌球蛋白轻链激酶和 Rho 相关激酶 II 的协调调节。总的来说，这项研究揭示了一个以前未知的机制——足突玫瑰花结的形成。
