Rap1 GTPase调节粘附的结位定位和细胞粘附
Andrea L Knox1, Nicholas H Brown
1Wellcome/CRC Institute and Department of Anatomy, University of Cambridge, Cambridge CB2 1QR, UK.
概括
小型瓜诺辛三酸酶Rap1活跃地保持了表皮细胞中细胞结点分布的均性. 没有Rap1,接口会错位,破坏细胞行为和组织完整性.
科学领域:
- 细胞生物学 细胞生物学
- 皮质生物学 皮质生物学
- 分子生物学分子生物学
背景情况:
- 细胞-细胞结合点,特别是粘附结合点,对于上皮组织完整性至关重要.
- 它们在细胞周围的均分布对于正常的上皮组织至关重要.
- 调节附着结位置的分子机制尚未完全理解.
研究的目的:
- 研究在上皮细胞中粘附结的均分布的分子机制.
- 确定小瓜诺辛三酸酶Rap1在粘附结位定位中的作用.
- 为了了解受损的接接口分布的功能后果.
主要方法:
- 利用基因操纵来创建具有Rap1.1突变的细胞.
- 通过显微镜观察和分析了野生类型和Rap1-突变细胞中的粘附结分布.
- 在野生类型上皮质环境中评估突变细胞克隆的行为和组织整合.
主要成果:
- 附着结的均分布是一个活跃的,依赖Rap1的过程.
- 缺乏Rap1的细胞在一侧表现出凝结的附着结.
- 干扰的附着结位定位导致异常的上皮细胞行为和克隆分散.
- 拉普1定位在粘附结处,可能有助于细胞分裂后的重新密封.
结论:
- 小型瓜诺三酸酶Rap1对于维持上皮细胞中适当的附着结点定位至关重要.
- 拉普1的失调会影响上皮细胞的行为,组织完整性和细胞定位.
- 通过Rap1调节的附着结位定位可能会影响细胞的移动性和分裂动态.
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...
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:
Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...


