Cell migration without a lamellipodium: translation of actin dynamics into cell movement mediated by tropomyosin.
Cell migration without a lamellipodium: translation of actin dynamics into cell movement mediated by tropomyosin.
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DOI：
10.1083/jcb.200406063
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发表时间：
2005-02-14
影响因子：
7.8
通讯作者：
Waterman-Storer, Clare M
中科院分区：
文献类型：
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作者：
Gupton, Stephanie L;Anderson, Karen L;Kole, Thomas P;Fischer, Robert S;Ponti, Aaron;Hitchcock-DeGregori, Sarah E;Danuser, Gaudenz;Fowler, Velia M;Wirtz, Denis;Hanein, Dorit;Waterman-Storer, Clare M
肌动蛋白细胞骨架受局部调控，以实现细胞运动的功能特化。利用定量荧光散斑显微镜(QFSM)对迁移的上皮细胞，我们以前定义了两个不同的F-肌动蛋白网络基于它们的F-肌动蛋白结合蛋白和不同的F-肌动蛋白周转和运动模式。Lipellidium由快速依赖聚合的逆流的踏板状F-肌动蛋白阵列组成，含有高浓度的Arp2/3和ADF/cofilin，而板层则表现出空间上随机的F-肌动蛋白组装和拆解点状，由肌球蛋白介导的缓慢逆流，并含有肌球蛋白II和原肌球蛋白(TM)。在本文中，我们将骨骼肌αTM显微注射到上皮细胞中，通过定量荧光显微镜、电子显微镜和免疫定位显示，这抑制了功能性片状磷脂的形成。片状脂肪抑制的细胞表现出持续的前沿突起和快速的细胞迁移。抑制内源Long TM亚型改变了突起的持久性。因此，细胞可以通过抑制片状脂体进行迁移，我们认为TM是迁移细胞中F-肌动蛋白功能专门化的主要调节因子。
The actin cytoskeleton is locally regulated for functional specializations for cell motility. Using quantitative fluorescent speckle microscopy (qFSM) of migrating epithelial cells, we previously defined two distinct F-actin networks based on their F-actin–binding proteins and distinct patterns of F-actin turnover and movement. The lamellipodium consists of a treadmilling F-actin array with rapid polymerization-dependent retrograde flow and contains high concentrations of Arp2/3 and ADF/cofilin, whereas the lamella exhibits spatially random punctae of F-actin assembly and disassembly with slow myosin-mediated retrograde flow and contains myosin II and tropomyosin (TM). In this paper, we microinjected skeletal muscle αTM into epithelial cells, and using qFSM, electron microscopy, and immunolocalization show that this inhibits functional lamellipodium formation. Cells with inhibited lamellipodia exhibit persistent leading edge protrusion and rapid cell migration. Inhibition of endogenous long TM isoforms alters protrusion persistence. Thus, cells can migrate with inhibited lamellipodia, and we suggest that TM is a major regulator of F-actin functional specialization in migrating cells.