GABAA受体 π形成了通过依赖G蛋白的通路刺激ERK的通道
Yueyue Wang1, Yalan Zhang2, Wenxue Li3
1Yale Cancer Biology Institute, Yale University, West Haven, CT 06516, USA; Breast Medical Oncology, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Molecular cell
|December 6, 2024
概括
γ-氨基黄油酸A型受体子单元π (GABRP) 通过G蛋白合通路激活癌症生长,而不是直接的离子流. 了解它的结构和功能为癌症治疗提供了新的目标.
科学领域:
- 分子和细胞生物学分子和细胞生物学
- 癌症研究 癌症研究
- 神经科学是一个神经科学.
背景情况:
- γ-氨基黄油酸A型受体子单元π (GABRP) 与癌症生长有关.
- 它的信号通路,特别是通过细胞外调节激酶 (ERK),仍然没有特征.
研究的目的:
- 确定GABRP在癌症中的信号传递的结构和功能机制.
- 为了阐明GABRP刺激癌症生长的途径.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 确定了GABRP在原生纳米磁盘中的结构.
- 进行了功能性测试,以评估GABRP对GABA结合的反应.
主要成果:
- 在结构上与其他GABAARs相似,GABRP形成同型体,在封闭和开放状态之间过渡.
- GABRP主要通过G蛋白合途径发出信号来激活ERK,而不是通过生理GABA水平的化物流.
- 仅在超生理学GABA度时才观察到离子otropic活性.
结论:
- GABRP的功能类似于一个metabotropic受体,不同于典型的电离子 GABAARs.
- 这项研究为在GABRP阳性癌症中准GABRP提供了结构和功能基础.
- 将GABRP的生长信号与其离子变功能脱开来,开辟了新的治疗策略.
相关概念视频
IP3/DAG Signaling Pathway
11.9K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
11.9K
G-Protein Gated Ion Channels
4.5K
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...
Sensory...
4.5K
Antiepileptic Drugs: GABAergic Pathway Potentiators
328
γ-aminobutyric acid or GABA, plays a pivotal role as an inhibitory neurotransmitter in the brain. GABA pathway potentiators, also known as GABAergic drugs, are a class of pharmaceutical agents designed to enhance the functioning of the GABAergic system. These medications primarily treat epilepsy, a neurological disorder characterized by recurrent seizures.
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for...
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for...
328
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.1K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.1K
GPCRs Regulate Adenylyl Cylase Activity
5.3K
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...
5.3K
Amplifying Signals via Second Messengers
6.7K
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
6.7K


