GONADOTROPIN BETA SUBUNITS DETERMINE THE RATE OF ASSEMBLY AND THE OLIGOSACCHARIDE PROCESSING OF HORMONE DIMER IN TRANSFECTED CELLS
GONADOTROPIN BETA SUBUNITS DETERMINE THE RATE OF ASSEMBLY AND THE OLIGOSACCHARIDE PROCESSING OF HORMONE DIMER IN TRANSFECTED CELLS
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DOI：
10.1083/jcb.104.5.1173
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发表时间：
1987-05-01
影响因子：
7.8
通讯作者：
BOIME, I
中科院分区：
文献类型：
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作者：
CORLESS, CL;MATZUK, MM;BOIME, I
糖蛋白激素促黄体激素（LH）和绒毛膜促性腺激素（CG）共享由相同的α-氨基端组成的共同结构。亚基非共价连接到一个酶特异性β上。亚单位LH在垂体前叶产生，CG在胎盘合成。为了比较人LH和CG在相同细胞类型中的组装、加工和分泌，我们在小鼠C-127乳腺肿瘤细胞中单独和一起表达了它们的亚基。转染克隆的分析揭示了一个意想不到的差异，个别表达的亚基的分泌。而α和CG β。亚基被快速和定量地分泌，只有10%的新合成的LH β。亚基到达介质。剩余的亚基存在于细胞内的糖苷内切酶H（endo H）敏感性库中，其周转率为λ。8小时与α的共表达亚基导致LH β的“拯救”。亚基通过形成LH二聚体，其被有效地分泌。然而，LH β的组合。 与α是缓慢的，尽管存在过量的α，但总效率仅为50%。相比之下，CG β.与α迅速组装在一起。合成后的亚基。两个. beta。亚基对组合α的N-连接寡糖加工的影响也不同。LH二聚体的寡糖对内源性H不敏感，而CG二聚体的寡糖对内源性H部分敏感。因此，尽管LG β和LG β之间具有高度的同源性。和CG β，这两种亚基的不同之处在于它们作为游离亚基的分泌、它们与α的组装速率、以及它们与α的组装速率。亚基的N-连接寡糖加工的影响，以及它们对组合α-亚基的N-连接寡糖加工的影响。
The glycoprotein hormones lutropin (LH) and chorionic gonadotropin (CG) share a common structure consisting of an identical .alpha. subunit noncovalently linked to a hormone-specific .beta. subunit. While LH is produced in the anterior pituitary, CG is synthesized in placenta. To compare the assembly, processing, and secretion of human LH and CG in the same cell type, we have expressed their subunits, individually and together, in mouse C-127 mammary tumor cells. Analysis of transfected clones revealed an unexpected difference in the secretion of individually expressed subunits. Whereas .alpha. and CG.beta. subunits were rapidly and quantitatively secreted, only 10% of newly synthesized LH.beta. subunit reached the medium. The remaining subunit was found in an intracellular, endoglycosidase H (endo H)-sensitive pool that had a turnover rate of .apprx. 8 h. Coexpression with .alpha. subunit resulted in "rescue" of LH.beta. subunit by formation of LH dimer, which was efficiently secreted. However, combination of LH.beta. with .alpha. was slow, with an overall efficiency of only 50% despite the presence of excess .alpha.. In contrast, CG.beta. was rapidly assembled with the .alpha. subunit after synthesis. The two .beta. subunits also differed in their influence on the N-linked oligosaccharide processing of combined .alpha.. The oligosaccharides of LH dimer were endo H resistant, while those of CG dimer remained partially endo H sensitive. Thus, despite a high degreee of homology between LG.beta. and CG.beta., the two subunits differ in their secretion as free subunits, their rate of assembly with .alpha. subunit, and in their effect on the N-linked oligosaccharide processing of combined .alpha.