TRPC5通道与多囊素蛋白的相互相互作用
Misun Kwak1, Hana Kang1, Jinhyeong Kim1
1Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
概括
多囊素-1 (PKD1) 通过G蛋白信号调节TRPC4/C5通道,其与PKD2的相互作用影响TRPC5通道活性和内皮细胞功能,这表明多囊性病的新治疗标.
科学领域:
- 细胞生物学 细胞生物学
- 离子通道生理学 离子通道生理学
- 分子医学是分子医学.
背景情况:
- 聚素-1 (PKD1) 对细胞过程至关重要,与内皮细胞中的PKD2和TRPC通道相互作用.
- 之前的研究探讨了PKD1-TRPC4和PKD2-TRPC1的相互作用,但PKD2在调节其他TRPC通道中的作用仍然不清楚.
研究的目的:
- 阐明PKD2在调节TRPC通道活性,特别是TRPC4和TRPC5.5中的作用.
- 研究内皮细胞中PKD1,PKD2和TRPC通道 (TRPC1,TRPC4,TRPC5) 之间的复杂相互作用.
- 基于这些相互作用,探索多囊性病的潜在治疗点.
主要方法:
- 用G蛋白信号调制来评估TRPC4/C5通道的激活.
- 在PKD1.1存在或不存在的情况下调查TRPC通道转移和活性.
- 同免疫沉试验用于研究PKD2和TRPC通道复合体的形成.
- 电生理学记录用于测量离子通道电流.
- 西方涂抹分析STAT蛋白质酸化.
主要成果:
- PKD1通过G蛋白信号激活TRPC4和TRPC5通道,独立于通道转位.
- PKD2是由TRPC5向血膜,但不是TRPC1,并与TRPC1和TRPC5.5形成复合体.
- PKD2调节TRPC5通道活性,影响细胞内信号传递和STAT酸化,而PKD2和TRPC1在TRPC5结合方面竞争.
结论:
- 通过G蛋白调节,PKD1调节TRPC4/C5通道的活动.
- PKD2与TRPC5相互作用,影响其局部化和功能,并与TRPC1竞争TRPC5结合.
- 针对TRPC5通道提供了一种潜在的治疗策略,用于改善多囊性脏疾病中的血管内皮功能.
相关概念视频
Cotranslational Protein Translocation
7.2K
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
7.2K
Protein Translocation Machinery on the ER Membrane
4.5K
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
4.5K
Tight Junctions
5.2K
Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
5.2K
Vesicular Tubular Clusters
2.4K
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...
2.4K
Mechanically-gated Ion Channels
6.2K
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
6.2K
Assembly of Signaling Complexes
5.7K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.7K


