由于FCHO2产生的膜曲率激活了Nedd4L泛素酶,Nedd4L泛素酶被激活了
Yasuhisa Sakamoto1, Akiyoshi Uezu1, Koji Kikuchi1
1Department of Molecular Pharmacology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Kumamoto, 860-8556, Japan.
The EMBO journal
|October 14, 2024
概括
这种 ubiquitin 结合酶 Nedd4LL.
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:
- Nedd4L (一种全方位基因酶) 通过修改像ENaC这样的货物蛋白来控制内细胞分裂.
- Nedd4L的催化活性受到其自身的C2和HECT域的抑制.
- 目前尚不清楚Nedd4L激活的机制.
研究的目的:
- 为了研究Nedd4L在内细胞分裂过程中如何被激活.
- 探索FCHO2和膜曲率在Nedd4L调节中的作用.
主要方法:
- 在细胞中对Nedd4L和FCHO2进行同局部研究.
- 在体外复制FCHO2-Nedd4L相互作用.
- 对ENaC的Nedd4L无化和内细胞的分析.
- 膜曲率测试. 膜曲率测试. 膜曲率测试. 膜曲率测试.
主要成果:
- FCHO2对于Nedd4L介导的全方位化和ENaC内细胞分裂是必不可少的.
- Nedd4L与FCHO2在克拉涂层坑中局部化,并由FCHO2 BAR域激活.
- FCHO2诱导的Nedd4L激活和招募是由膜曲率驱动的,而不是蛋白质相互作用.
- 在Nedd4L C2域感知膜曲率,以缓解自身抑制.
结论:
- 由FCHO2产生的膜曲率直接激活了Nedd4L.
- 这项研究揭示了在内细胞分裂过程中通过膜形状激活酶的新机制.
相关概念视频
Mechanisms of Membrane-bending
2.6K
The living membranes are flexible due to their fluid mosaic nature; however, their bending into different shapes is an active process regulated by specific lipids and proteins. The membrane bending can be transient as seen in vesicles or stable for a long time as in microvilli. Cells regulate the size, location, and duration of the membrane curvature.
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
2.6K
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
Pinching-off of Coated Vesicles
3.1K
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.1K
Export of Misfolded Proteins out of the ER
3.5K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.5K
Cell Motility through Blebbing
1.9K
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...
1.9K
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


