皮肤干细胞通过通过GSK3β调节微管-ACF7连接来协调定向迁移
Xiaoyang Wu1, Qing-Tao Shen, Daniel S Oristian
1The Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, Rockefeller University, New York, NY 10065, USA.
Cell
|February 8, 2011
概括
干细胞 (SCs) 使用Wnt信号来指导伤口愈合期间的迁移. 研究人员发现GSK3β激酶酸化物ACF7,控制微管-动因相互作用对于SC运动至关重要.
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:
- 干细胞 (SC) 迁移对于恒温和伤口愈合至关重要.
- Wnt信号通路调节SC活动和定向迁移.
- 细胞骨动态对于细胞的运动和功能至关重要.
研究的目的:
- 调查Wnt信号如何与干细胞中的细胞骨动力学集成.
- 在毛囊干细胞 (HF-SCs) 中识别GSK3β激酶的下游标.
- 阐明ACF7酸化在调节微管 - 动因相互作用和细胞迁移中的作用.
主要方法:
- 通过GSK3β. ,对ACF7的酸化位点进行映射.
- 对具有改变酸化状态的ACF7突变的分析.
- 在ACF7-零皮肤模型中评估微管架构和细胞迁移.
- 在伤口修复期间的SC迁移的体内研究.
主要成果:
- 在HF-SC中,GSK3β直接化ACF7,这是一个微管子-动因交联蛋白质.
- 酸化使ACF7从微管中脱离,影响微管架构.
- 极化细胞运动需要ACF7的动态酸化.
- ACF7,但不是构成性酸化的ACF7,在ACF7-无皮肤中恢复极化微管的生长和SC迁移.
结论:
- 通过GSK3β介导的ACF7酸化是一种关键的调节机制,它将Wnt信号与细胞骨动力学相结合.
- 在伤口修复过程中,ACF7的动态光调节对于极化干细胞迁移至关重要.
- ACF7充当关键的支架,将信号通路与细胞骨组织联系起来,以指导细胞运动.
相关概念视频
01:32Cytoskeletal Coordination in Cell Migration
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 proteins that...
01:09Cell Migration
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.
01:19Cell Migration
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.
01:24Microtubules in Cell Motility
Microtubules are thick hollow cylindrical proteins that help form the cytoskeleton. Microtubules have varied roles in the cell. These filaments help form cellular appendages like cilia and flagella, which are responsible for locomotion. The cilia arise from basal bodies, separated from the main body by a membrane-like structure forming the transition zone. This zone is the gate for the entry of lipids and proteins, creating a unique composition of lipids and proteins in the ciliary membrane and...
01:16Cell Motility through Blebbing
Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Blebbing Through the Matrix
In multicellular...
01:21Chemotaxis and Direction of Cell Migration
Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon towards...