How do cells sense actin cortex-free membrane?
How do cells sense actin cortex-free membrane?
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细胞如何感知无肌动蛋白皮质的膜？
DOI：
10.1080/15384101.2016.1204860
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发表时间：
2016
期刊：
影响因子：
4.3
通讯作者：
Ikenouchi J
中科院分区：
文献类型：
--
作者：
K. Miyagi;Y. Kitagawa;M. Asaoka;R. Teramoto;Y. Natori;T. Saito;M. Nakano;Ikenouchi J
细胞膜总是与下面的肌动蛋白细胞骨架相关联。在胞质分裂或凋亡期间，细胞内压力增加或肌动蛋白细胞骨架的破坏导致质膜从细胞骨架脱离，并且质膜的突起被动形成。这些膜突起被称为膜泡。直到最近，膜泡没有被深入研究。然而，已经积累了许多生物体使用动态膜泡作为运动工具的具体证据。1此外，最近的研究表明，某些类型的癌细胞在某些条件下采用大的极化膜泡进行迁移和侵袭。2这种细胞迁移模式被称为“变形虫”迁移。上皮-间质转化（EMT）被认为是癌细胞获得侵袭性表型的主要原因。然而，敲除EMT所必需的转录因子的癌细胞也表现出侵袭和转移，这表明存在EMT非依赖性的癌症侵袭机制。3一种这样的EMT非依赖性侵袭机制是基于泡的细胞迁移。因此，了解与膜泡相关的分子机制具有重要的生物学和临床意义。然而，对膜泡调控的分子机制的理解仍处于起步阶段。膜泡的周期起始于质膜从下面的细胞骨架上脱离。无肌动蛋白皮质的膜由于细胞内的静水压力而被动地突出。在扩张阶段结束时，肌动蛋白丝开始局部积聚。然后，肌动蛋白丝逐渐覆盖整个突出的膜。最后，肌球蛋白II和肌球蛋白轻链被募集到肌动蛋白皮质，由于肌动蛋白-肌球蛋白皮质的收缩活性，膜泡收缩（图1）。这些过程似乎很简单，然而，有许多未解决的问题，关于肌动蛋白皮层和质膜之间的动态相互作用。其中，核心问题是肌动蛋白皮质的重组是如何在突出的膜上启动的。Charras等人在2006年首次仔细研究了肌动蛋白皮质重组的过程。[4]在这篇开创性的论文中，他们证明了肌动蛋白丝的调节因子以分阶段的方式被募集到质膜上。这项研究和随后的研究表明，表皮生长因子受体途径底物8（Eps 8）和ezrin/radixin/moesin（ERM）家族蛋白迅速移动到质膜之前，在扩张阶段结束时的肌动蛋白丝的再生长。Eps 8是一种肌动蛋白加帽和肌动蛋白捆绑蛋白。ERM家族蛋白是连接质膜和肌动蛋白细胞骨架的锚定蛋白。当在Thr 567磷酸化时，ERM家族蛋白采取开放形式。我们最近发现，ERM家族蛋白的激活发生在收缩的开始，是必不可少的快速再生的肌动蛋白皮质。5
The cell membrane is always associated with the underlying actin cytoskeleton. During cytokinesis or apoptosis, increased intracellular pressure or destruction of the actin cytoskeleton leads to detachment of the plasma membrane from the cytoskeleton and protrusions of the plasma membrane are passively formed. These membrane protrusions are termed membrane blebs. Until recently, membrane blebs were not intensively studied. However, concrete evidence that many organisms use dynamic membrane blebs as a tool for locomotion has accumulated. 1 Furthermore, recent studies revealed that some types of cancer cells adopt large polarized membrane blebs for migration and invasion under certain conditions. 2 This mode of cell migration is called “amoeboid” migration. Epithelial-mesenchymal transition (EMT) was assumed to be the primary cause of cancer cells acquiring an invasive phenotype. However, cancer cells in which transcription factors essential for EMT are knocked out also exhibit invasion and metastasis, suggesting the existence of EMT-independent mechanisms of cancer invasion. 3 One such EMT-independent invasion mechanism is bleb-based cell migration. Therefore, understanding the molecular mechanisms associated with membrane blebs is biologically and clinically important. However, understanding of the molecular mechanisms involved in the regulation of membrane blebs is still in its infancy. The cycle of membrane blebs initiates when the plasma membrane detaches from the underlying cytoskeleton. The actin cortex-free membrane passively protrudes due to the intracellular hydrostatic pressure. At the end of the expansion phase, actin filaments start to locally accumulate. Then, actin filaments gradually cover the entire protruded membrane. Finally, myosin II and myosin light chain are recruited to the actin cortex, and membrane blebs retract due to the contractile activity of the acto-myosin cortex (Fig. 1). These processes seem to be quite simple; however, there are many unsolved issues regarding the dynamic interplay between the actin cortex and plasma membrane. Among them, the central question is how reassembly of the actin cortex is initiated at the protruded membrane.The processes of actin cortex reassembly were first closely examined by Charras et al. in 2006. 4 In this seminal paper, they demonstrated that regulators of actin filaments are recruited to the plasma membrane in a staged manner. This study and subsequent studies revealed that epidermal growth factor receptor pathway substrate 8 (Eps8) and ezrin/radixin/moesin (ERM) family proteins rapidly move to the plasma membrane prior to the regrowth of actin filaments at the end of the expansion phase. Eps8 is an actin-capping and actin-bundling protein. ERM family proteins are anchoring proteins that connect the plasma membrane and actin cytoskeleton. ERM family proteins adopt an open form when phosphorylated at Thr567. We recently found that activation of ERM family proteins occurs at the onset of retraction and is essential for the rapid regrowth of the actin cortex. 5