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

我们之前报道了人促黄体激素受体的一个剪接变体[hLHR(Dexon 9)]，它缺少外显子9，编码靠近第一跨膜结构域的N末端细胞外环。最近的一些研究表明，G蛋白偶联受体(GPCRs)能够形成受体的二聚化或寡聚化，这增加了hLHR(Dexon 9)与野生型黄体生成素受体(HLHR)之间发生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hLHR是否与hLHR(Dexon 9)形成联系。HLHR(Dexon 9)与hLHR未成熟带(68 KDa)相互作用，而与成熟带(85 KDa)不相互作用。当hLHR和hLHR(Dexon 9)共同表达时，hLHR的表达密度明显低于单独表达的hLHR。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，内化指数略有下降。在这项研究中，我们证明了人促黄体生成素受体能够形成受体复合体。我们的发现可能扩大了人类黄体生成素受体的剪接变异体特异性地调节野生型人类黄体生成素受体功能特性的可能性。

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.