对Arp2/3复合体的抑制信号引导细胞迁移
Irene Dang1, Roman Gorelik, Carla Sousa-Blin
11] Group Cytoskeleton in Cell Morphogenesis, Laboratoire d'Enzymologie et Biochimie Structurales, CNRS UPR3082, Gif-sur-Yvette 91190, France [2].
Nature
|October 18, 2013
概括
一种新发现的蛋白质Arpin作为Arp2/3复合体的抑制剂,对细胞迁移至关重要. 它的耗尽增强了细胞的速度和方向的持续性,揭示了细胞运动方向性的关键调节器.
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:
- 细胞迁移对于发育和疾病至关重要,它依赖于动态的活性蛋白网络,用于lamellipodia中的血突起.
- Arp2/3 复合体核酸分支的行为因网络,其由Rac GTPase 下游的 WAVE 蛋白激活,驱动了 lamellipodia 形成.
- 控制细胞迁移方向性的机制尚不完全理解.
研究的目的:
- 为了确定细胞迁移方向性的新型调节者.
- 在细胞迁移的背景下,描述一种新发现的蛋白质Arpin的功能.
- 阐明Arpin与已知途径如Rac-WAVE-Arp2/3在控制细胞运动中的相互作用.
主要方法:
- 在体外生化测试以确定Arpin对Arp2/3复合体的抑制作用.
- 在哺乳动物细胞中的耗尽研究 (例如,使用siRNA) 来评估Arpin在细胞迁移速度和方向性中的作用.
- 在鱼类皮质细胞中进行微注射实验,观察Arpin操纵对细胞转变行为的影响.
- 对Dictyostelium discoideum进行的研究证实了Arpin的保留作用.
主要成果:
- 在实验室中,Arpin被确定为Arp2/3复合物的抑制剂.
- 拉斯信号招募和激活Arpin在状脚尖端,类似于WAVE.
- 阿尔宾的耗尽导致了拉梅利波迪亚突起速度的增加和整体细胞迁移速度的增加.
- 阿尔宾的枯竭导致哺乳动物细胞和Dictyostelium中更直的细胞迁移轨迹.
- 在高度持久的鱼类角细胞迁移中,Arpin微注射诱导了转向行为.
结论:
- 阿尔作为Rac激活的Arp2/3复合物的抑制剂,在调节细胞迁移方面发挥着关键作用.
- 在控制细胞迁移的方向性和持久性方面,Arpin抑制途径和WAVE激活途径之间的平衡至关重要.
- 阿尔宾代表了一种保护的机制,用于控制不同物种和细胞类型的细胞运动.
相关概念视频
01:09Cell Migration
16.6K
Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
16.6K
01:19Cell Migration
6.1K
Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
6.1K
01:21Cell Polarization by Rho Proteins
3.2K
Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
3.2K
01:17Intracellular Signaling Affects Focal Adhesions
2.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.8K
01:32Cytoskeletal Coordination in Cell Migration
4.9K
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.9K
01:18Role of Myosin in Cell Migration
2.8K
Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction....
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction....
2.8K