膜活性GTPases在涂层囊泡形成中的保存功能
Thomas J Pucadyil1, Sandra L Schmid
1Department of Cell Biology, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
概括
涂层囊泡使用自我组装的蛋白质和GTPases,如Arf和dynamin用于细胞内运输. 这些蛋白质管理货物包装和囊泡释放,确保有效的分子输送.
科学领域:
- 细胞生物学 细胞生物学
- 分子和细胞生物学分子和细胞生物学.
- 生物化学 生物化学
背景情况:
- 涂层囊泡对于细胞内运输,缩和包装货物分子至关重要.
- 皮层蛋白 (克拉特林,适应器复合体,COPI,COPII) 和GTPases (Arf,Sar1,dynamin) 驱动囊泡形成和膜变形.
- GTPases以一种依赖于GTP的方式与膜结合并重塑膜.
研究的目的:
- 探索Arf家族GTPases和dynamin在涂层囊泡形成和功能中的作用.
- 在货物包装和囊泡释放中研究Arf GTPases和dynamin之间的机械相似性.
主要方法:
- 对最近关于囊泡贩运中GTPase功能的证据的文献综述.
- 对Arf GTPases和dynamin的结构多样性和机制作用的分析.
- 专注于GTPase介导的膜改造和货物捕获.
主要成果:
- 尽管有结构上的差异,Arf GTPases和dynamin具有功能上的相似之处.
- 这两种GTPase类型都作为货物包装和囊泡成熟的忠实性监测器.
- 它们还被认为是囊泡裂变机制的组成部分,调解释放.
结论:
- 阿尔夫GTPases和dynamin在调节涂层囊泡动力学方面发挥着保留作用.
- 它们作为忠实度监测器和囊泡裂变中的功能突出显示了它们在细胞内运输中的重要性.
- 了解这些GTPases可以了解货物分类和囊泡贩运的精确机制.
相关概念视频
Coat Assembly and GTPases
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Pinching-off of Coated Vesicles
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...
Clathrin Coated Vesicles
Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
COP Coated Vesicles
Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of different...
Rab Proteins
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...
Rab Cascades
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.


