RGS-PX1,GalphaS的GAP和排序nexin在囊泡贩运中的一个GAP
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093-0651, USA.
概括
调节G蛋白信号传递 (RGS) 蛋白调节细胞信号传递. 一种新发现的RGS蛋白,RGS-PX1,作为Galpha的GTPase激活蛋白 (GAP) 起作用,并影响囊泡贩运.
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 生物化学
背景情况:
- 异构三聚体GTP结合蛋白 (G蛋白) 是关键的信号转换器.
- 调节G蛋白信号传递 (RGS) 蛋白质通过作为GTPase激活蛋白 (GAPs) 来调节G蛋白信号传递的持续时间和幅度.
研究的目的:
- 识别和描述涉及G蛋白信号传递的新型RGS蛋白质.
- 调查RGS-PX1在G蛋白信号传递和囊泡贩运中的双功能作用.
主要方法:
- 蛋白相互作用研究证实RGS-PX1与Galpha结合.
- GTPase活性测试测量RGS-PX1在Galpha上的GAP活性.
- 基于细胞的测试,以评估RGS-PX1对表皮生长因子受体 (EGF受体) 降解的影响.
主要成果:
- RGS-PX1被确定为一种特定于Galpha的GAP.
- RGS-PX1的RGS域与Galpha直接相互作用并加速其GTP水解,减弱Galpha介导的信号传输.
- RGS-PX1包含一个Pox (PX) 域,类似于排序nexin (SNX) 蛋白.
- RGS-PX1的表达延迟了EGF受体的溶酶体降解.
结论:
- RGS-PX1具有双重功能,作为一种特定于Galpha的GAP和一种具有排序nexin类属性的蛋白质.
- RGS-PX1可以作为异构三基G蛋白信号通路和囊泡贩运过程之间的分子链接.
相关概念视频
Overview of Secretory Vesicles
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...
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...
Vesicular Tubular Clusters
After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
With the help of motor proteins such...
Transport Across the Golgi
While it is unclear how molecules move between adjacent Golgi cisternae, it is apparent that the molecules move from cis- cisterna, the entry face, to the trans- cisterna, the exit face. Experiments initially suggested vesicles that bud from one cisterna and fuse with the next cisterna to transport proteins between the cisternae. This vesicular transport model describes the Golgi apparatus as a relatively static structure with a unique enzyme composition in each cisterna. Molecules are...
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.


