竞争和协同Arp2/3和formins在核活动波中的竞争和协同作用
Xiang Le Chua1, Chee San Tong1, Maohan Su2
1Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Biological Sciences, Centre for Bioimaging Sciences, Singapore 117557, Singapore.
Cell reports
|July 5, 2024
概括
在GTPase Cdc42.42驱动的活性波中,甲基素先于Arp2/3复合体. 通过SHIP1,Arp2/3通过SHIP1对抗formins和Cdc42,揭示了复杂的活性调节反循环.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生化学
- 生物物理学的生物物理.
背景情况:
- 动蛋白组合和动态是细胞结构和功能的基础.
- 剖析特定的actin调节蛋白的作用是具有挑战性的,因为actin的广泛影响.
- 巨细胞中的动因波提供了一个模型系统来研究动因动力学.
研究的目的:
- 为了研究在actin波传播过程中actin调节蛋白的顺序招募.
- 阐明GTPase Cdc42和formins在活动波形成中的作用.
- 了解Arp2/3复合体和formin/Cdc42通路之间的对抗关系.
主要方法:
- 活细胞对巨细胞中的活性波的成像.
- 使用光显微镜分析蛋白质招募动态.
- 基因操纵以研究蛋白质功能 (例如,构成性活跃突变).
- 生物化学测定用于研究蛋白质相互作用和调节.
主要成果:
- 在阿丁波中的Arp2/3复合体之前,Formin (FMNL1,mDia3) 被招募.
- GTPase Cdc42的相互作用驱动FMNL1的振荡,而活跃的Cdc42/FMNL1可以独立形成波.
- 通过SHIP1.1,Arp2/3复合体通过竞争上游Cdc42调节来对抗FMNL1和活性Cdc42.
- Arp2/3通过SHIP1招募来负面调节Cdc42水平,影响FMNL1活动.
结论:
- 这项研究揭示了一种新的调节机制,它涉及素和Arp2/3复合体在动因波动力学中的作用.
- 复杂的反循环涉及Cdc42,formins,Arp2/3和SHIP1的控制行为细胞骨架网络.
- 这为基于actin的细胞过程的精确时空调节提供了洞察力.
相关概念视频
Generation of Straight or Branched Actin Filaments
2.9K
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
2.9K
Actin Polymerization
6.5K
Actin polymerization occurs through the head-to-tail association of binding sites on monomeric actin or G-actin to form filamentous or F-actin. The polymerization can be divided into three phases ̶ nucleation, elongation, and steady-state phase.
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight...
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight...
6.5K
Formation of Higher-order Actin Filaments
3.0K
The polymerization of G-actin monomers into filamentous F-actin is a multi-step process. Once the F-actins are formed, they can bundle together in different arrangements to form higher-order networks and regulate cellular functions. Common examples include the formation of lamellipodia and filopodia at the cell's leading edge by actin reorganization in a migrating cell. The microvilli on the brush border epithelial cells are also formed through the F-actin network.
The high-order actin...
The high-order actin...
3.0K
Mechanism of Lamellipodia Formation
2.5K
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
2.5K
Mechanism of Filopodia Formation
2.3K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.3K
Actin Filament Depolymerization
3.1K
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
3.1K


