Splice variant Human LH receptor modulates the function of wild type Human LH receptor

剪接变体人 LH 受体调节野生型人 LH 受体的功能

• 批准号: 13671695
• 负责人: NAKAMURA Kazuto
• 金额: $ 1.22万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671695/
• 关键词: LH receptor; dimerization

We previously reported a splice variant form of human LH receptor [hLHR(Dexon 9)] that lacks exon 9 coding the N-terminal extracellular loop close to the first transmembrane domain. Several recent studies suggest G protein-coupled receptors (GPCRs) are able to form dimerization or oligomerization of receptor, which raises the possibility of an intermolecular interaction between hLHR(Dexon 9) and the wild-type LH receptor (hLHR). The aim of this study is to test whether hLHR could form the association with hLHR(Dexon 9), by a co-immunoprecipitation study. An interaction between hLHR(Dexon 9) with the immature band (68 kDa) of hLHR and not with the mature band (85 kDa) was seen. When hLHR and hLHR(Dexon 9) were co-expressed, the density of hLHR expression was significantly reduced as compared to hLHR expressed alone. The hCG-stimulated cAMP accumulation in cells expressing hLHR(Dexon 9) was also impaired, compared to cells expressing hLHR. A small decrease in the internalization index was observed in cells co-expressing both hLHR and hLHR(Dexon 9). In this study, we demonstrated human LH receptor is capable of forming receptor complexes. Our findings may expand the possibility that a splice variant of human LH receptor specifically modulates the functional property of the wild-type human LH receptor.

我们之前报道了人类 LH 受体 [hLHR(Dexon 9)] 的剪接变体形式，其缺乏编码靠近第一个跨膜结构域的 N 端细胞外环的外显子 9。最近的几项研究表明，G 蛋白偶联受体 (GPCR) 能够形成受体二聚化或寡聚化，这增加了 hLHR(Dexon 9) 和野生型 LH 受体 (hLHR) 之间分子间相互作用的可能性。本研究的目的是通过免疫共沉淀研究来测试 hLHR 是否可以与 hLH​​R(Dexon 9) 形成关联。观察到 hLHR (Dexon 9) 与 hLH​​R 的未成熟带 (68 kDa) 之间存在相互作用，但与成熟带 (85 kDa) 之间没有相互作用。当hLHR和hLHR(Dexon 9)共表达时，与单独表达hLHR相比，hLHR表达密度显着降低。与表达 hLHR 的细胞相比，表达 hLHR (Dexon 9) 的细胞中 hCG 刺激的 cAMP 积累也受到损害。在同时表达 hLHR 和 hLHR (Dexon 9) 的细胞中观察到内化指数小幅下降。在这项研究中，我们证明人类 LH 受体能够形成受体复合物。我们的研究结果可能扩大了人 LH 受体的剪接变体特异性调节野生型人 LH 受体功能特性的可能性。

项目成果

Minegishi T, et al.: "Molecular Cloning, Cellular Distribution and Regulation of Rat Steroidogenic Acute Regulatory Protein (StAR) in the Ovary"Journal of Reproduction and Development. 48(1). 1-15 (2002)

Minegishi T 等人：“大鼠卵巢中类固醇生成急性调节蛋白 (StAR) 的分子克隆、细胞分布和调节”生殖与发育杂志。

Inoue K, et al.: "Effect of Transforming Growth Factor β on the Expression of Luteinizing Hormone Receptor in Cultured Rat Granulosa Cells"Biology of Reproduction. 67. 610-615 (2002)

Inoue K 等人：“转化生长因子 β 对培养的大鼠颗粒细胞中促黄体激素受体表达的影响”，《生殖生物学》67. 610-615 (2002)。