MiniBAR/GARRE1 是一个双 Rac 和 Rab 效应器,对于纤毛发育是必不可少的
Murielle P Serres1, Ronan Shaughnessy1, Sophie Escot2
1Institut Pasteur, Université de Paris, CNRS UMR3691, Membrane Traffic and Cell Division Laboratory, 25-28 rue du Dr Roux, 75015 Paris, France.
Developmental cell
|October 24, 2023
概括
MiniBAR蛋白控制细胞结构和运输以形成乳毛. 它的耗尽导致短毛和发育缺陷,突出其在毛发生和预防毛病的关键作用.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 毛对细胞信号传递,感知和发育至关重要.
- 乳毛形成 (乳毛发育) 需要降低actin收缩性和适当的细胞内贩运.
- 在纤毛发育过程中这些过程之间的协调仍然不太清楚.
研究的目的:
- 为了识别和描述一种新型蛋白质,该蛋白质参与协调actin细胞骨动力学和膜贩运,用于纤维生成.
- 阐明这种蛋白质调节纤维生成的分子机制.
主要方法:
- 蛋白质的识别和表征 (MiniBAR,Rac1,Rab35) 的方法.
- 使用显微镜进行定位研究.
- 功能性试验涉及细胞培养和斑马鱼模型中的蛋白质耗尽.
- 活动细胞骨组织,收缩性和蛋白质贩运的分析 (IFT88,ARL13B).
主要成果:
- 一种新型蛋白质,MiniBAR (截断的BAR域蛋白) 被确定,它与Rac1和Rab35.5结合.
- MiniBAR局限于血和细胞内囊泡,在纤维膜具有动态脉冲.
- 由于Rac/Rho GTPase水平的变化,MiniBAR枯竭导致眼的缩短,增加了动肌素收缩性,并影响了IFT88/ARL13B的贩运.
- 斑马鱼胚胎的MiniBAR已经枯竭,表现出短毛和类似毛病的症状,包括左右不对称的缺陷.
结论:
- MiniBAR 作为 Rac 和 Rab GTPases 的双效应剂.
- 它整合了调节行动蛋白细胞骨和膜贩运通路的调节,这对于纤维生成至关重要.
- MiniBAR功能障碍有助于纤毛病,强调其在纤毛形成和功能中的关键作用.
相关概念视频
Rab Proteins
4.0K
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...
4.0K
Mechanism of Lamellipodia Formation
2.6K
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...
2.6K
Rab Cascades
2.7K
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.
2.7K
Cell Polarization by Rho Proteins
2.7K
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,...
2.7K
Small GTPases - Ras and Rho
4.0K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
4.0K
Mechanism of Filopodia Formation
2.4K
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...
2.4K


