通过 Prickle2 LIM 域的压力动蛋白结合及其在全长蛋白质中的调节
bioRxiv : the preprint server for biology
|June 12, 2025
概括
普里克尔2 (Pk2) 的LIM域含区域 (LCR) 结合了应激的活性丝,但全长的Pk2却没有. 蛋白质域调节这种相互作用,的变体破坏了actin结合.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 发育生物学 发展生物学
背景情况:
- 细胞通过细胞骨蛋白感知机械压力.
- 众所周知,LIM域可以结合应激的活性纤维.
- 在全长蛋白中LIM域相互作用的调节尚不清楚.
研究的目的:
- 在全长蛋白质中研究LIM域-actin相互作用的调节.
- 确定Prickle2 (Pk2) 如何与压力下的酸纤维相互作用.
- 检查Pk2域在调节活性蛋白结合和细胞局部化中的作用.
主要方法:
- 研究了Xenopus mesoderm,以观察蛋白质局部化.
- 执行了Prickle2 (Pk2) 域的结构功能分析.
- 分析了人类患者衍生的Pk2.2变体.
主要成果:
- Pk2 的 LIM 域含有区域 (LCR) 与应激的活性纤维相关.
- 全长Pk2没有显示类似的招募应激的actin纤维.
- Pk2的PET域和C终端区域抑制了LCR的动蛋白招募,但促进了节点招募;变体损害了动蛋白结合.
结论:
- Pk2的结构域调节了其LIM域含区域 (LCR) 招募到酸纤维的过程.
- 特定的Pk2域调节了应激性actin和富含蛋白质的节点之间的局部化.
- 患者衍生的变体破坏了Pk2-actin相互作用,为疾病机制和平面细胞极性提供了洞察力.
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 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
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
Introduction to Actin
5.0K
Actin is a highly conserved cytoskeletal protein found abundantly in eukaryotic cells. It constitutes 10% weight of the total cellular protein in muscle cells, while in non-muscle cells, it is lower and makes up around 1–5 percent of the total cell protein. Actin found in the unicellular amoebae and complex multicellular animals is around 80% similar, demonstrating their conservation over a billion years of evolution. Actin coding genes are conserved within species and across...
5.0K
Cytoskeletal Linker Proteins - Plakins
2.3K
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
2.3K
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


