内细胞分裂驱动在原生同表达的GPCRs之间积极的cAMP信号歧视
Emily E Blythe1,2, Rita R Fagan1, Mark von Zastrow1,3,4
1Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, USA.
bioRxiv : the preprint server for biology
|July 16, 2025
概括
G蛋白结合受体 (GPCR) 在它们的内化能力上有所不同,产生不同的cAMP信号代码. 这种由内分细胞形成驱动的过程会影响下游的信号传输和细胞信息处理.
科学领域:
- 细胞生物学 细胞生物学
- 分子药理学分子药理学
- 生物物理学的生物物理.
背景情况:
- G蛋白结合受体 (GPCRs) 在激活时启动信号级联.
- 在受体内部化 (内细胞化) 后,GPCR信号的第二阶段可能会发生.
- 在激活后,GPCRs的内部化率呈现出显著的变化.
研究的目的:
- 调查GPCR内部化的差异如何影响下游信号配置文件.
- 阐明内细胞分裂在塑造cAMP信号动态中的作用.
- 为了比较三个共同表达的Gs-合的GPCRs与不同的内化行为之间的信号传递.
主要方法:
- 使用的人类胚胎细胞内源地表达三个Gs合的GPCRs:腺素-2B受体 (非内化),血管活性肠受体-1 (快速内化) 和β2-上腺素受体 (不那么快速内化).
- 分析了血膜和内分泌体中的cAMP生产动态.
- 研究了通过细胞质和核蛋白激酶A (PKA) 活动的下游信号传递.
主要成果:
- 每个GPCR都产生了一个独特的信号配置,通过其内细胞贩运来区分.
- 已经证明,内细胞分裂能调节cAMP产生的量和持续时间.
- 通过受体内部化建立了独特的时空cAMP代码,影响下游PKA激活.
结论:
- GPCR内细胞分解作为生物信息处理机制,将化学信号转化为时空cAMP代码.
- 这个过程包括将GPCRs感知到的信息压缩成由顺序PKA活动处理的代码.
- 这些发现表明GPCR信号传输和用于模式识别的计算自编码器网络之间存在类似之处.
更多相关视频
相关概念视频
G Protein-coupled Receptors
13.5K
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...
13.5K
Transducer Mechanism: G Protein–Coupled Receptors
2.5K
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,...
GPCRs are also called heptahelical,...
2.5K
G-protein Coupled Receptors
121.5K
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.
121.5K
GPCRs Regulate Adenylyl Cylase Activity
5.9K
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...
5.9K
GPCR Desensitization
6.5K
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...
6.5K
Activation and Inactivation of G Proteins
7.7K
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...
7.7K


