Dynamin 2 and BAR domain protein pacsin 2 cooperatively regulate formation and maturation of podosomes
Dynamin 2 and BAR domain protein pacsin 2 cooperatively regulate formation and maturation of podosomes
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DOI：
10.1016/j.bbrc.2021.07.041
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发表时间：
2021-07-27
影响因子：
3.1
通讯作者：
Takeda，Tetsuya
中科院分区：
文献类型：
--
作者：
Li，Jianzhen;Fujise，Kenshiro;Takeda，Tetsuya
Podosomes是在多种细胞类型（例如单核细胞或癌细胞）中形成的富含肌动蛋白的粘附结构，以促进细胞外基质（ECM）的附着和降解。先前的研究表明，发动蛋白2，一个大的GT3参与膜重塑和肌动蛋白组织，是所需的足体功能。在这项研究中，我们确定了一个BAR（Bin-Amphiphysin-Rvs 167）结构域蛋白pacsin 2作为动力蛋白2的功能伙伴在podosomes。发动蛋白2和pacsin 2相互作用并共定位于Src转化的NIH 3 T3（NIH-Src）细胞中的podosomes。NIH-Src细胞中的dynamin 2或pacsin 2的RNAi抑制了podosome的形成和成熟，表明podosome中的重要和相关作用。一致的是，pacsin 2的RNAi阻止了发动蛋白2定位于podosomes，并且发动蛋白2的相互RNAi阻止了pacsin 2定位于podosomes。综合这些结果，我们得出结论，动力蛋白2和pacsin 2协同调节NIH-Src细胞中的podosomes的组织。
Podosomes are actin-rich adhesion structures formed in a variety of cell types, such as monocytic cells or cancer cells, to facilitate attachment to and degradation of the extracellular matrix (ECM). Previous studies showed that dynamin 2, a large GTPase involved in membrane remodeling and actin organization, is required for podosome function. However, precise roles of dynamin 2 at the podosomes remain to be elucidated.In this study, we identified a BAR (Bin-Amphiphysin-Rvs167) domain protein pacsin 2 as a functional partner of dynamin 2 at podosomes. Dynamin 2 and pacsin 2 interact and co-localize to podosomes in Src-transformed NIH 3T3 (NIH-Src) cells. RNAi of either dynamin 2 or pacsin 2 in NIH-Src cells inhibited podosome formation and maturation, suggesting essential and related roles at podosomes. Consistently, RNAi of pacsin 2 prevented dynamin 2 localization to podosomes, and reciprocal RNAi of dynamin 2 prevented pacsin 2 localization to podosomes. Taking these results together, we conclude that dynamin 2 and pacsin 2 co-operatively regulate organization of podosomes in NIH-Src cells.