Arp2/3 complex inhibitors adversely affect actin cytoskeleton remodeling in the cultured murine kidney collecting duct M-1 cells.
Arp2/3 complex inhibitors adversely affect actin cytoskeleton remodeling in the cultured murine kidney collecting duct M-1 cells.
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DOI：
10.1007/s00441-013-1710-y
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发表时间：
2013-12
影响因子：
3.6
通讯作者：
Negulyaev, Yuri A.
中科院分区：
文献类型：
--
作者：
Ilatovskaya, Daria V.;Chubinskiy-Nadezhdin, Vladislav;Pavlov, Tengis S.;Shuyskiy, Leonid S.;Tomilin, Viktor;Palygin, Oleg;Staruschenko, Alexander;Negulyaev, Yuri A.
肌动蛋白细胞骨架的动态重塑在细胞迁移和活细胞中的各种信号传导过程中发挥着重要作用。控制真核细胞中新肌动蛋白丝成核的关键因素之一是肌动蛋白相关蛋白 2/3 (Arp2/3) 复合物。最近，发现并描述了两类新型小分子，它们与 Arp2/3 复合物上的不同位点结合并抑制其使 F-肌动蛋白成核的能力。当前的研究旨在研究 CK-0944666 (CK-666) 及其类似物（CK-869 和失活的 CK-689）对皮质集合管细胞系 M-1 中肌动蛋白微丝重组的影响。我们已经证明，用 CK-666 和 CK869 处理会导致 F-肌动蛋白重组，并极大地影响细胞运动率。本研究中使用的化合物浓度 (100-200 μM) 既不会导致细胞活力丧失，也不会影响细胞形状或单层完整性；因此，所述化合物的作用并非由于结构副作用。因此，我们在此得出结论，Arp2/3 复合物在 M-1 细胞的细胞运动和 F-肌动蛋白重组中发挥重要作用。此外，CK-666 及其类似物是研究 Arp2/3 复合体的有用工具。
Dynamic remodeling of the actin cytoskeleton plays an essential role in cell migration and various signaling processes in the living cells. One of the critical factors that controls the nucleation of new actin filaments in eukaryotic cells is the actin related protein 2/3 (Arp2/3) complex. Recently, two novel classes of small molecules that bind to different sites on the Arp2/3 complex and inhibit its ability to nucleate F-actin have been discovered and described. The current study was aimed at investigating the effects of CK-0944666 (CK-666) and its analogs (CK-869 and inactive CK-689) on the reorganization of the actin microfilaments in the cortical collecting duct cell line, M-1. We have shown that treatment with CK-666 and CK869 results in the reorganization of F-actin and drastically affects cell motility rate. The concentrations of the compounds used in this study (100-200 μM) neither cause loss of cell viability nor influence cell shape or monolayer integrity; hence the effects of described compounds were not due to the structural side effects. Therefore, we conclude here that the Arp2/3 complex plays an important role in cell motility and F-actin reorganization in M-1 cells. Furthermore, CK-666 and its analogs are useful tools for the investigation of the Arp2/3 complex.
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影响因子：
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作者：
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