通过离子对视网膜棒 guanylate cyclase进行高度合作的反控制
1Department of Cell Biology, Stanford University School of Medicine, California 94305.
Nature
|July 7, 1988
概括
降低视网膜棒细胞中的水平显著增加了酸环酶活性,这对于暴露于光线后恢复视力至关重要. 这一发现强调了的含量.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 视网膜棒细胞的视觉刺激涉及一个级联减少循环GMP (cGMP) 和关闭通道.
- 黑暗状态的恢复需要cGMP重合成,由瓜尼酸环酶催化.
- 在照明后降低细胞质 (Cai) 被假设刺激瓜尼酸环酶活性.
研究的目的:
- 为了研究水平对酸环酸酶活性在棒外段的作用.
- 阐明对视力恢复中酸环酸酶调节的机制.
主要方法:
- 在不同度下测量牛杆外段中的酸环酶活性.
- 研究一种可溶性蛋白质在依赖的瓜尼酸环酶激活中的作用.
- 使用低盐的缓冲冲洗来释放和重新添加与膜相关的蛋白质.
主要成果:
- 当从200nM降低到50nM时,未照明的牛杆外段中的关酸环酶活性增加了5-20倍.
- 这种依赖的反应呈现出急剧的合作反应,希尔系数为3.9.
- 低盐缓冲释放的可溶性蛋白质调解了敏感性,通过重新添加它可以部分恢复.
结论:
- 关酸环酶活性对杆子外部段的生理水平高度敏感.
- 一种蛋白质因子通过光诱导的减少来调解酸环酸酶的合作激活.
- 这种由对酸甲酸环酶的光依赖调节对于在视觉刺激后恢复黑暗电流至关重要.
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 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...
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Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
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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.
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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
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