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

我们先前报道了一种剪接变体形式的人LH受体[hLHR（Dexon 9）]，其缺少编码靠近第一跨膜结构域的N-末端细胞外环的外显子9。最近的一些研究表明，G蛋白偶联受体（GPCR）能够形成受体的二聚体或寡聚体，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检测hLHR是否可以与hLHR（Dexon 9）形成缔合。观察到hLHR（Dexon 9）与hLHR的未成熟条带（68 kDa）之间的相互作用，而不与成熟条带（85 kDa）相互作用。当hLHR和hLHR（Dexon 9）共表达时，与单独表达的hLHR相比，hLHR表达的密度显著降低。与表达hLHR的细胞相比，表达hLHR的细胞（Dexon 9）中hCG刺激的cAMP蓄积也受损。在共表达hLHR和hLHR（Dexon 9）的细胞中观察到内化指数的小幅降低。在这项研究中，我们证明了人LH受体能够形成受体复合物。我们的研究结果可能会扩大的可能性，人类LH受体的剪接变异体特异性调节野生型人类LH受体的功能特性。

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.