通过与WASP相关的活性脱聚合蛋白N-WASP诱导filopodium形成
1Department of Biochemistry, Institute of Medical Science, University of Tokyo, Japan.
Nature
|January 9, 1998
概括
蛋白Cdc42 (细胞分裂控制蛋白42) 与N-WASP (神经维斯科特-阿尔德里奇综合征蛋白) 结合,从而触发行为线的形成. 这种相互作用对于产生filopodia至关重要,与其他已知的Cdc42结合蛋白不同.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- Cdc42,一个Rho家族的GTPase,调节了actin动态和filopodia形成.
- 虽然有几种蛋白质与Cdc42结合,但它们在Cdc42诱导的类动物中的作用尚不清楚.
- 在结构上,WASP (威斯科特-阿尔德里奇综合征蛋白) 与N-WASP相似,但不介导Cdc42诱导的类.
研究的目的:
- 为了研究Cdc42诱导filopodia形成的机制.
- 为了确定Cdc42的特定结合伙伴,这对filopodia产生至关重要.
- 为了阐明N-WASP在Cdc42-介导的氨酸重塑中的作用.
主要方法:
- 细胞中Cdc42和N-WASP的同时表达.
- 无细胞的活性蛋白聚合试验.
- 亚丁微尖形成的分析.
主要成果:
- N-WASP,但不是WASP,当与活性Cdc42.2共同表达时,会诱导长长的活性微尖.
- 活性Cdc42结合暴露了N-WASP的活性脱聚合区域.
- 结合Cdc42刺激了N-WASP的乙烯酸脱聚合活性,促进了乙烯酸聚合.
结论:
- 对N-WASP的Cdc42结合对于启动filopodia形成至关重要.
- N-WASP作为Cdc42在actin细胞骨架组织中的作用的关键调解者.
- Cdc42和N-WASP之间的相互作用通过N-WASP的actin-depolymerizing活性来调节actin聚合.
相关概念视频
Actin Polymerization
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 actin...
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 actin...
Generation of Straight or Branched Actin Filaments
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...
Actin Filament Depolymerization
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...
Actin Polymerization and Cell Motility
Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate.
Mechanism of Filopodia Formation
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...
Mechanism of Lamellipodia Formation
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...


