The formin FRL1 (FMNL1) is an essential component of macrophage podosomes.
The formin FRL1 (FMNL1) is an essential component of macrophage podosomes.
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DOI：
10.1002/cm.20468
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发表时间：
2010-09
期刊：
影响因子：
2.9
通讯作者：
Blystone, Scott D.
中科院分区：
文献类型：
--
作者：
Mersich, Akos T.;Miller, Matthew R.;Chkourko, Halina;Blystone, Scott D.
足小体是骨髓系细胞和一些转化细胞中高度动态的富含肌动蛋白的粘附结构。与转化的间充质细胞类型不同，足体是巨噬细胞中唯一的粘附结构，因此介导与粘附底物的所有接触，包括穿过复杂组织的运动以进行免疫监视。炎症巨噬细胞和转化细胞类型中足体的存在表明其在组织侵袭中发挥重要作用。足体的蛋白质组、组装和维护正在兴起，但仍不完全确定。之前，我们报道了与巨噬细胞β-3整合素相关的福尔明同源序列和肌动蛋白组装活性。在本研究中，我们通过定量 RT-PCR 和蛋白质印迹证明，formin FRL1 在单核细胞分化为巨噬细胞期间特异性上调。我们发现福尔马林 FRL1 定位于初级巨噬细胞足体富含肌动蛋白的核心。 FRL1 与 beta-3 整合素共沉淀，固定细胞和活细胞荧光显微镜显示内源性和过表达的 FRL1 选择性定位于巨噬细胞足体。 siRNA 对 FRL1 的靶向破坏导致细胞粘附减少和足体动力学破坏。我们的数据表明，FRL1 负责修饰巨噬细胞足小体的肌动蛋白，并可能参与组织内粘附和迁移过程中的肌动蛋白细胞骨架动力学。
Podosomes are highly dynamic actin-rich adhesion structures in cells of myeloid lineage and some transformed cells. Unlike transformed mesenchymal cell types, podosomes are the sole adhesion structure in macrophage and thus mediate all contact with adhesion substrate, including movement through complex tissues for immune surveillance. The existence of podosomes in inflammatory macrophages and transformed cell types suggest an important role in tissue invasion. The proteome, assembly, and maintenance of podosomes are emerging, but remain incompletely defined. Previously, we reported a formin homology sequence and actin assembly activity in association with macrophage β-3 integrin. In this study we demonstrate by quantitative RT-PCR and Western blotting that the formin FRL1 is specifically upregulated during monocyte differentiation to macrophages. We show that the formin FRL1 localizes to the actin-rich cores of primary macrophage podosomes. FRL1 co-precipitates with beta-3 integrin and both fixed and live cell fluorescence microscopy show that endogenous and overexpressed FRL1 selectively localize to macrophage podosomes. Targeted disruption of FRL1 by siRNA results in reduced cell adhesion and disruption of podosome dynamics. Our data suggest that FRL1 is responsible for modifying actin at the macrophage podosome and may be involved in actin cytoskeleton dynamics during adhesion and migration within tissues.
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