Structural and functional plasticity of the luteinizing hormone/choriogonadotrophin receptor.
Structural and functional plasticity of the luteinizing hormone/choriogonadotrophin receptor.
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DOI：
10.1093/humupd/dmt023
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发表时间：
2013-09
影响因子：
13.3
通讯作者：
B. Troppmann;G. Kleinau;G. Krause;J. Gromoll
中科院分区：
文献类型：
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作者：
B. Troppmann;G. Kleinau;G. Krause;J. Gromoll
背景近年来发现，促黄体生成素/绒毛膜促性腺激素受体(LHCGR)存在多种类型。除了啮齿动物中已知的经典受体类型外，灵长类动物和人类中还存在一种含有额外外显子的LHCGR类型。这个特定的外显子6A在转录水平上引入了一条迄今未知的LHCGR调控途径，可以导致仅覆盖细胞外部分的替代蛋白的表达。此外，在新世界灵长类动物谱系中已描述了一种在mRNA和蛋白质水平上缺乏外显子10的LHCGR类型，导致了另一种受体类型，其中连接富含亮氨酸的重复结构域和跨膜结构域的细胞外铰链区的氨基酸缺失。方法利用Medline/PubMed系统检索主题相关信息。结构同源性模型从糖蛋白激素受体网络应用程序和最近的出版物中检索。结果在一种新的方法中，我们结合LHCGR的功能特征和三维特性以及不同的受体类型来推断这两个参数之间的因果关系。在此基础上，推断了不同类型LHCGR的生理影响和病理生理后果。结论不同类型的LHCGR和相应的两种激素(促黄体生成素和卵泡刺激素)组成的复杂系统是今后研究选择性激素结合、信号转导和受体调节的主要挑战。这些自然产生的LHCGR类型的存在需要重新审视我们目前对受体功能、实验设置和数据解释的看法，但也提供了干扰人类促黄体生成素/促性腺激素释放激素作用的新的临床方法。
BACKGROUND In recent years it became evident that several types of the luteinizing hormone/choriogonadotrophin receptor (LHCGR) exist. In addition to the classical receptor type known in rodents, an LHCGR type containing an additional exon is present in primates and humans. This specific exon 6A introduces a hitherto unknown regulatory pathway of the LHCGR at the transcriptional level which can lead to the expression of an alternative protein covering the extracellular part only. Furthermore, an LHCGR type lacking exon 10 at the mRNA and protein levels has been described in the New World primate lineage, giving rise to an additional receptor type in which amino acids of the extracellular hinge region connecting the leucine-rich repeat domain and transmembrane domain are missing. METHODS Topic-related information was retrieved by systematic searches using Medline/PubMed. Structural homology models were retrieved from a glycoprotein hormone receptors web application and from recent publications. RESULTS In a novel approach, we combine functional aspects with three-dimensional properties of the LHCGR and the different receptor types to deduce causative relationships between these two parameters. On this basis, the physiological impact and patho-physiological consequences of the different LHCGR types are inferred. CONCLUSIONS The complex system of different LHCGR types and two corresponding hormones (LH and CG) represents a major challenge for future studies on selective hormone binding, signal transduction and receptor regulation. The presence of these naturally occurring LHCGR types requires re-examining of our present view on receptor function, experimental set-ups and data interpretation, but also offers new clinical approaches to interfere with LH/CG action in humans.