细胞胀增强了联结体驱动的β-上腺素信号传递
Alexei Sirbu1, Marc Bathe-Peters1, Jothi L M Kumar2
1Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Nature communications
|September 6, 2024
概括
透性胀会改变细胞环境,增强G蛋白结合受体 (GPCR) 的活性. 这导致放大信号响应,表明受体受体调节的一般机制由生物物理上下文.
科学领域:
- 细胞生物物理学 细胞生物物理学
- 分子药理学分子药理学
- 膜生物学 膜生物学
背景情况:
- G蛋白结合受体 (GPCR) 是关键的细胞表面蛋白质,其功能受到其膜环境的影响.
- GPCRs的构造状态决定了它们的活性和下游信号.
- 血内的微观相互作用在调节GPCR行为方面发挥着重要作用.
研究的目的:
- 为了研究透性胀对GPCR构造和功能的影响.
- 为了确定透性胀是否会改变完整细胞内的受体的生物物理环境.
- 为了评估因透性胀而改变的受体构造的下游信号后果.
主要方法:
- 在完好无损的细胞中利用了透性胀作为类刺激.
- 监测β2-上腺素受体 (一个原型的GPCR) 的功能反应.
- 测量下游信号,特别是cAMP的产生,作为对上腺刺激的反应.
- 在包括成人心肌细胞在内的初级细胞类型中得到验证的结果.
主要成果:
- 透性胀的细胞促进β2-上腺体受体的活性构造.
- 上腺刺激在胀的细胞导致cAMP短暂反应的幅度显著增加.
- 观察到的信号增强在像成人心肌细胞这样的初级细胞类型中得到了验证.
- 有证据表明,这种机制不仅限于β2-上腺素受体.
结论:
- 受体功能的细微调节由细胞膜的生物物理背景.
- 透性胀作为GPCR介导下游信号的增强剂.
- 这表明一个一般的调节机制,其中细胞生物物理变化影响受体活性和信号结果.
相关概念视频
GPCRs Regulate Adenylyl Cylase Activity
5.4K
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...
5.4K
Adrenergic Receptors: β Subtype
1.6K
β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
1.6K
Intracellular Signaling Affects Focal Adhesions
2.6K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.6K
Endocrine Signaling
64.1K
Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
64.1K
GPCR Desensitization
5.9K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
5.9K
Secondary Messengers in Hormone Action
2.1K
Water-soluble hormones cannot cross the plasma membrane, so they rely on protein receptors that span the membrane to trigger intracellular signaling pathways. These pathways then activate second messengers inside the cell, including cAMP or calcium ions.
Many hormones bind to transmembrane G protein-coupled receptors that connect to regulatory G proteins. These G proteins can then activate enzymes such as adenylyl cyclase or phospholipase C. Adenylyl cyclase converts ATP to cAMP, activating...
Many hormones bind to transmembrane G protein-coupled receptors that connect to regulatory G proteins. These G proteins can then activate enzymes such as adenylyl cyclase or phospholipase C. Adenylyl cyclase converts ATP to cAMP, activating...
2.1K


