Association of human follitropin (FSH) receptor with splicing variant of human lutropin/choriogonadotropin receptor negatively controls the expression of human FSH receptor.
Association of human follitropin (FSH) receptor with splicing variant of human lutropin/choriogonadotropin receptor negatively controls the expression of human FSH receptor.
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DOI：
10.1210/me.2005-0049
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发表时间：
2005-08
影响因子：
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通讯作者：
Soichi Yamashita;Kazuto Nakamura;Yuki Omori;K. Tsunekawa;M. Murakami;T. Minegishi
中科院分区：
文献类型：
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作者：
Soichi Yamashita;Kazuto Nakamura;Yuki Omori;K. Tsunekawa;M. Murakami;T. Minegishi
人促黄体激素（LH）/绒毛膜促性腺激素（CG）受体[hLHR（外显子9）]的剪接变体，缺乏外显子9，以前克隆在一个正常的月经周期的妇女的黄体。通过去污剂可溶性结合试验和受体生物素化实验的支持，受体结合试验显示hLHR（外显子9）既不在细胞表面表达，也不具有与hCG结合的能力。此外，通过内切糖苷酶H处理证实hLHR（外显子9）存在于内质网（ER）中。免疫共沉淀实验清楚地表明，hLHR（外显子9）和组成型的hLHR，留在ER，形成与人促卵泡素（FSH）受体（hFSHR）的协会。这表明，在muplant-LHR的存在下，hFSHR，这是被困在ER和相关的hLHR（外显子9），是不能来到质膜。这种现象在促性腺激素受体中是特异性的，因为人TSH受体不能被免疫共沉淀。此外，这种受体复合物减弱了细胞内的hFSHR受体蛋白水平，这损害了cAMP的产生。为了阐明这种受体复合物降低hFSHR蛋白的机制，我们进行了Percoll分级实验，表明受体复合物将hFSHR驱动到溶酶体而不是质膜。这些结果揭示了FSHR表达调控的新机制。
A splice variant of human lutropin (LH)/choriogonadotropin (CG)-receptor [hLHR(exon 9)] that lacks exon 9 was previously cloned in the corpus luteum of a woman with a normal menstrual cycle. Supported by a detergent-soluble binding assay and a receptor biotinylation experiment, the receptor binding assay shows hLHR(exon 9) is neither expressed at the cell surface nor has the capability of binding to hCG. In addition, hLHR(exon 9) was confirmed in the endoplasmic reticulum (ER) by endoglycosidase H treatment. A coimmunoprecipitation experiment clearly showed that hLHR(exon 9) and constitutively inactivate mutant-LHRs, which stay in the ER, form an association with the human follitropin (FSH)-receptor (hFSHR). This suggests that in the presence of mutant-LHR, hFSHR, which is trapped in the ER and associated with hLHR(exon 9), is unable to come up to the plasma membrane. This phenomenon is specific among gonadotropin receptors because human TSH receptor failed to be coimmunoprecipitated. Furthermore, this receptor complex attenuated the hFSHR receptor protein level within the cells, which impaired cAMP production. To elucidate the mechanism underlying the decrease in hFSHR protein by this receptor complex, we performed a Percoll fractionation experiment, which indicated that the receptor complex drove hFSHR to the lysosome instead of the plasma membrane. These results reveal a novel mechanism of FSHR expression regulation.