MC4R Dimerization in the Paraventricular Nucleus and GHSR/MC3R Heterodimerization in the Arcuate Nucleus: Is There Relevance for Body Weight Regulation?
MC4R Dimerization in the Paraventricular Nucleus and GHSR/MC3R Heterodimerization in the Arcuate Nucleus: Is There Relevance for Body Weight Regulation?
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DOI：
10.1159/000334903
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发表时间：
2012-01-01
影响因子：
4.1
通讯作者：
Biebermann, Heike
中科院分区：
文献类型：
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作者：
Rediger, Anne;Piechowski, Carolin Leonie;Biebermann, Heike
世界范围内的肥胖流行正在增加，但在这个时候，没有长效和具体的药物治疗。外周激素信号通过激活弓状核（ARC）中相应的受体将代谢状态传达给下丘脑。在这个大脑区域，表达了多种可能参与体重调节的G蛋白偶联受体（GPCR），但到目前为止，大多数下丘脑GPCR的详细功能仅部分了解。GPCR的一个重要且未被充分认识的特征是通过二聚化和异二聚化进行调节的能力。越来越多的证据表明GPCR的异源二聚化导致了深远的功能后果。最近，我们可以证明黑皮质素3受体（MC 3R）和生长激素促分泌素受体（GHSR）-1a的相互作用导致两种受体的功能调节。虽然GPCR-GPCR相互作用在下丘脑中的生理作用尚未阐明，但这一概念为研究和理解依赖于GPCR信号的下丘脑功能提供了新的途径。由于GPCR是对抗许多疾病的药物的重要靶标，因此异二聚体的鉴定可能是高度特异性药物的先决条件。因此，有必要详细了解这些机制及其在体重调节中的作用。这种理解的基础是下丘脑核团中GPCR-GPCR在能量代谢中的相互作用。在这篇综述中，我们总结了黑皮质素受体和GHSR-1a在下丘脑体重调节，特别是因为它们涉及到可能的药物靶点的现有知识。此外，我们包括现有的证据GPCR二聚化的参与和意义。版权所有（C）2012 S. Karger AG，巴塞尔
The worldwide obesity epidemic is increasing, yet at this time, no long-acting and specific pharmaceutical therapies are available. Peripheral hormonal signals communicate metabolic status to the hypothalamus by activating their corresponding receptors in the arcuate nucleus (ARC). In this brain region, a variety of G protein-coupled receptors (GPCRs) are expressed that are potentially involved in weight regulation, but so far, the detailed function of most hypothalamic GPCRs is only partially understood. An important and underappreciated feature of GPCRs is the capacity for regulation via di- and heterodimerization. Increasing evidence implicates that heterodimerization of GPCRs results in profound functional consequences. Recently, we could demonstrate that interaction of the melanocortin 3 receptor (MC3R) and the growth hormone secretagogue receptor (GHSR)-1a results in a modulation of function in both receptors. Although the physiological role of GPCR-GPCR interaction in the hypothalamus is yet to be elucidated, this concept promises new avenues for investigation and understanding of hypothalamic functions dependent on GPCR signaling. Since GPCRs are important targets for drugs to combat many diseases, identification of heterodimers may be a prerequisite for highly specific drugs. Therefore, a detailed understanding of the mechanisms and their involvement in weight regulation is necessary. Fundamental to this understanding is the interplay of GPCR-GPCR in the hypothalamic nuclei in energy metabolism. In this review, we summarize the current knowledge on melanocortin receptors and GHSR-1a in hypothalamic weight regulation, especially as they pertain to possible drug targets. Furthermore, we include available evidence for the participation and significance of GPCR dimerization. Copyright (C) 2012S. Karger AG, Basel