小型GTP结合蛋白rab4控制了内细胞通路上的早期分类事件
P van der Sluijs1, M Hull, P Webster
1Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
Cell
|September 4, 1992
概括
Rab4蛋白调节内体循环和液相内细胞分裂. 过度表达野生型Rab4会降低液体吸收并改变转移素受体循环,影响铁的运输.
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 生化学
背景情况:
- Rab4是一种ras类型的GTP结合蛋白.
- Rab4以细胞周期依赖的方式与早期内体结合.
研究的目的:
- 研究Rab4在内细胞通路中的作用.
- 确定Rab4过度表达对内分细胞,溶酶体运输和循环的影响.
主要方法:
- 产生过度表达野生型或突变型Rab4的稳定细胞系.
- 测量流体阶段内细胞分裂和转移素受体 (Tfn-R) 循环.
- 对转移素 (Tfn) 和Tfn-R在内基因组内的局部化进行分析.
主要成果:
- 过度表达野生类型的Rab4使流体相内细胞形成减少了三倍.
- 过度表达Rab4改变了Tfn-R的循环,导致从内体到血膜的再分配.
- 铁释放被阻止,防止Tfn传递到酸性早期内分泌体,导致Tfn在非酸性囊泡中积累.
结论:
- Rab4在控制循环过程中涉及的内分体的功能和形成方面发挥着至关重要的作用.
- Rab4影响了内细胞通路内的货物的分类和运输.
- 这些发现表明,Rab4是内体体贩运和受体循环的关键调节者.
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相关概念视频
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
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...
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...
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
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.
Small GTPases - Ras and Rho
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:
