GPR162是一种β细胞CART受体
Andreas Lindqvist1, Mia Abels1, Liliya Shcherbina1
1Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for Experimental Medical Science, Lund University, CRC, Malmö, Sweden.
iScience
|December 11, 2023
概括
胰腺β细胞中的可卡因和胺调节转录 (CART) 信号由G蛋白结合受体162 (GPR162) 介导. 这项研究确定GPR162是CART受体,对胰岛素分泌和细胞骨调节至关重要.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 众所周知,可卡因和胺调控转录 (CART) 会影响胰腺小岛的胰岛素分泌.
- 胰腺β细胞中CART的特定受体尚未确定.
- 之前的工作确定了CART在人类和动物小岛上的胰岛素作用.
研究的目的:
- 为了识别胰腺β细胞中介于CART作用的受体.
- 研究G蛋白结合受体162 (GPR162) 在CART信号传输中的作用.
- 阐明CART影响胰岛素分泌和细胞功能的机制.
主要方法:
- 卡普特敲除INS-1 832/13细胞的RNA测序以确定潜在的受体.
- 结合试验包括近距离结合试验,放射性结合和共同免疫沉,以确认CART-GPR162相互作用.
- Gpr162敲击实验,以评估对CART介导效应的功能影响.
- 分析胰岛素分泌和细胞骨的安排,以应对CART刺激.
主要成果:
- 通过RNA测序,GPR162被确定为最受Cartpt调节的受体.
- 通过使用多项生化和近距离测定,证实了CART与GPR162的结合.
- Gpr162的淘汰导致了CART结合的减少,CART诱导的表细胞分裂的减弱,以及胰岛素分泌的减少.
- 发现了CART在调节细胞骨结构中的新型GPR162依赖性作用.
结论:
- G蛋白结合受体162 (GPR162) 被确定为胰腺β细胞中可卡因和胺调节转录 (CART) 的功能受体.
- GPR162调解了CART对胰岛素分泌,外细胞和细胞骨组织的影响.
- 这些发现为CART调节的β细胞功能提供了关键的机制性见解.
相关概念视频
Transducer Mechanism: G Protein–Coupled Receptors
2.0K
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,...
2.0K
G Protein-coupled Receptors
12.1K
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...
12.1K
G-protein Coupled Receptors
119.5K
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.
119.5K
Activation and Inactivation of G Proteins
7.2K
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...
7.2K
GPCR Desensitization
6.1K
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...
6.1K
GPCRs Regulate Adenylyl Cylase Activity
5.6K
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...
5.6K


