质子感应G蛋白合受体
Marie-Gabrielle Ludwig1, Miroslava Vanek, Danilo Guerini
1Novartis Institutes for Biomedical Research, CH-4002 Basel, Switzerland.
Nature
|September 5, 2003
概括
新的研究确定卵巢癌G蛋白结合受体1 (OGR1) 是一种对pH稳定至关重要的质子感应受体. 这一发现揭示了调节血液pH水平的分子机制.
科学领域:
- 生理学 生理学 生理学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 血液pH值通过呼吸和脏机制严格调节,约为7.4.
- 规范pH稳态的精确分子通路尚不完全理解.
- 骨架充当缓冲体,骨质母细胞对pH值的变化做出反应,但它们的感知机制尚不清楚.
研究的目的:
- 为了识别参与pH平衡的新型分子参与者.
- 研究卵巢癌G蛋白结合受体1 (OGR1) 在pH感应中的作用.
- 探索GPR4和OGR1在骨细胞中的功能.
主要方法:
- 位点定向的突变发生,以识别pH感应中的关键氨基酸.
- 检测因诺酸盐和循环AMP的形成,以应对pH的变化.
- 免疫组织化学检测OGR1在老鼠组织中的表达.
主要成果:
- OGR1作为质子感应受体,在pH值6.8和7.8.8之间激活异醇酸盐的形成.
- 在OGR1的细胞外表面上胺残留物对于pH感应至关重要.
- 相关受体GPR4也感知pH值,但调节周期性AMP水平.
- OGR1在骨髓瘤细胞,骨质母细胞前体,骨质母细胞和骨细胞中表达,调解pH依赖的信号.
结论:
- OGR1和GPR4被确定为关键的质子感应受体.
- 这些受体在维持生理学pH平衡中起着重要作用.
- OGR1与骨系统中的pH感应有关,特别是在骨质母细胞和骨细胞中.
相关概念视频
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
G-Protein Gated Ion Channels
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Sensory organs,...
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...


