Modulating effects of RAMPs on signaling profiles of the glucagon receptor family.
Modulating effects of RAMPs on signaling profiles of the glucagon receptor family.
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RAMP 对胰高血糖素受体家族信号传导谱的调节作用
DOI：
10.1016/j.apsb.2021.07.028
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Wang MW
中科院分区：
文献类型：
--
作者：
Shao L;Chen Y;Zhang S;Zhang Z;Cao Y;Yang D;Wang MW
受体活性调节蛋白(RAMP)是与特定的G蛋白偶联受体(GPCRs)形成复合体并调节其功能的辅助分子。RAMP与GPCRs的胰升糖素受体家族相互作用已被证实，但其潜在的机制尚不清楚。在这项研究中，我们使用了生物发光共振能量转移(BRET)的方法来全面研究这种相互作用。结合cAMP积聚、GαQ激活和β抑制蛋白1/2募集实验，我们不仅验证了以前报道的GPCRAMP对，而且发现了GPCRAMP相互作用的新模式。RAMP1能改变由GCGR和GLP1R引起的三个信号事件，RAMP2主要影响GCGR、GLP1R和GLP2受体对β-arrestin1/2的募集，而RAMP3对除生长激素释放激素受体外的所有家族成员都有广泛的负面影响。我们的结果表明，RAMP以受体特异性的方式调节G蛋白依赖性和非依赖性的高血糖素受体家族成员之间的信号转导。绘制这种相互作用的图谱为RAMP在配体识别和受体激活中的作用提供了新的见解。本研究确定了RAMP与GPCRs的胰升糖素受体家族之间的相互作用。CAMP积聚、GαQ激活和β-arrestin1/2募集的信号谱进一步表征了这种相互作用。
Receptor activity-modulating proteins (RAMPs) are accessory molecules that form complexes with specific G protein-coupled receptors (GPCRs) and modulate their functions. It is established that RAMP interacts with the glucagon receptor family of GPCRs but the underlying mechanism is poorly understood. In this study, we used a bioluminescence resonance energy transfer (BRET) approach to comprehensively investigate such interactions. In conjunction with cAMP accumulation, Gαq activation and β-arrestin1/2 recruitment assays, we not only verified the GPCR–RAMP pairs previously reported, but also identified new patterns of GPCR–RAMP interaction. While RAMP1 was able to modify the three signaling events elicited by both glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), and RAMP2 mainly affected β-arrestin1/2 recruitment by GCGR, GLP-1R and glucagon-like peptide-2 receptor, RAMP3 showed a widespread negative impact on all the family members except for growth hormone-releasing hormone receptor covering the three pathways. Our results suggest that RAMP modulates both G protein dependent and independent signal transduction among the glucagon receptor family members in a receptor-specific manner. Mapping such interactions provides new insights into the role of RAMP in ligand recognition and receptor activation. This study identified the interactome between RAMP and the glucagon receptor family of GPCRs. The interactions were further characterized by signaling profiles of cAMP accumulation, Gαq activation and β-arrestin1/2 recruitment.
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