拉尔小GTPase是外囊复合体在分泌中的重要调节者
bioRxiv : the preprint server for biology
|September 5, 2025
概括
这项研究表明Ral GTPase (RAL-1) 直接调节了C. elegans中的Exocyst复合体,影响了神经元发育和囊泡运输. 这些发现揭示了Ral在细胞生物学中的新作用.
科学领域:
- 细胞生物学
- 分子生物学
- 发育生物学
背景情况:
- 囊复合体对于甲动物的囊泡贩运至关重要,但其调节者尚未完全理解.
- 在外囊调节中涉及Ral GTPases,但对甲状动物的直接证据有限.
- 酵母外囊功能涉及Rab GTPases,但缺乏Ral GTPases.
研究的目的:
- 调查Ral GTPase (RAL-1) 在调节Caenorhabditis elegans中Exocyst复合物的直接作用.
- 阐明RAL-1-Exocyst相互作用的分子机制和生理后果.
- 建立C. elegans作为研究Ral-Exocyst通路的模型.
主要方法:
- 使用了Caenorhabditis elegans作为一个模型生物.
- 使用结构引导的基因组编辑来探测RAL-1-Exocyst接口.
- 评估了对神经元发育 (PVD树状植被) 和囊泡贩运的影响.
主要成果:
- 通过保留的结合部位证明了内源RAL-1与Exocyst复合物的直接接触.
- 表明RAL-1的丧失导致树树木的发育中断和囊泡的流通受损.
- 观察到RAL-1的细胞自主和非自主作用,影响神经元和上皮细胞.
- 通过编辑RAL-1-Exocyst接口生成的合成表型证实了功能重要性.
结论:
- 在体内,RAL-1 是甲状腺异囊复合体的真实调节者.
- Ral-Exocyst相互作用独立于其他分泌途径.
- 在多个生物尺度上解剖Ral-Exocyst机制提供了一个强大的系统.
相关概念视频
GTPases and their Regulation
8.6K
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,...
Large G-proteins,...
8.6K
Coat Assembly and GTPases
3.6K
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...
3.6K
Overview of Secretory Vesicles
8.6K
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
8.6K
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
Small GTPases - Ras and Rho
4.2K
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:
4.2K
Rab Proteins
4.1K
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...
4.1K


