对于内皮Weibel-Palade体外细胞形成,需要从外细胞中解离RalB
Moua Yang1,2, Alexandra Boye-Doe3, Mohammed Ali3
1Bloodworks Northwest Research Institute, Seattle, WA 98102.
Molecular biology of the cell
|April 2, 2025
概括
拉斯样B (RalB) GTPase通过调节外囊结合来调节韦贝尔-帕拉德体 (WPB) 外细胞分裂. RalB-GTP 从外囊脱离促进 WPB 释放,突出显示 RalB.
科学领域:
- 细胞生物学 细胞生物学
- 分子信号传递是分子信号传递.
- 内分泌学 在内分泌学.
背景情况:
- 拉斯样 (Ral) GTPases是细胞过程的关键调节者,包括外细胞形成,作为分子开关.
- 外囊复合体是Ral GTPases在调节外细胞形成中的关键效应因子.
- 韦贝尔-帕拉德体 (WPBs) 是专门的内皮分泌颗粒,储存威尔布兰德因子,对于静血至关重要.
研究的目的:
- 调查Ral异构体,特别是RalB在WPBs受调节的表细胞突变中的特定作用.
- 阐明RalB在WPB外细胞形成过程中与外囊复合体相互作用的机制.
- 确定RalB酸化对其与外囊和随后WPB释放的相互作用的影响.
主要方法:
- 利用基于细胞的测试来研究RalB在WPB外细胞形成中的必要性.
- 研究了RalB (GDP与GTP结合) 和外囊复合体之间的结合动态.
- 采用蛋白激酶C (PKC) 抑制和局部定向突变发生来评估RalB酸化的作用.
主要成果:
- 拉尔B,而不是拉尔A,对于受调节的WPB外细胞形成是必不可少的.
- 拉尔B在其GDP结合状态中结合了外部细胞,这是一个新的相互作用机制.
- 内皮细胞刺激导致RalB-GTP,导致外囊解并促进WPB结合和外细胞形成.
- 在RalB的C端高变区 (HVR) 的PKC依赖酸化增强了休息细胞中的外囊相互作用.
- 通过刺激,PKC抑制或特定突变,RalB的脱化会解开外囊并增加WPB的外细胞化.
结论:
- 外囊复合体与RalB的脱是促进内皮WPB外细胞形成的关键事件.
- 拉尔B酸化动态调节其与外囊的相互作用,影响WPB释放.
- 与RalA相比,RalB表现出不同的调节机制和潜在的独特功能,尽管它们具有同质性.
相关概念视频
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
Rab Cascades
2.6K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.6K
Rab Proteins
3.8K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
3.8K
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
Intralumenal Vesicles and Multivesicular Bodies
3.4K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.4K
Receptor-mediated Endocytosis
103.7K
Overview
103.7K


