Carboxypeptidase E is a regulated secretory pathway sorting receptor: Genetic obliteration leads to endocrine disorders in Cpe(fat) mice
Carboxypeptidase E is a regulated secretory pathway sorting receptor: Genetic obliteration leads to endocrine disorders in Cpe(fat) mice
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DOI：
10.1016/s0092-8674(00)81860-7
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发表时间：
1997-01-10
期刊：
影响因子：
64.5
通讯作者：
Loh, YP
中科院分区：
文献类型：
--
作者：
Cool, DR;Normant, E;Loh, YP
一种将分泌蛋白分选成颗粒以通过内分泌-神经内分泌细胞中的调节分泌途径释放的机制涉及将蛋白质结合到transGolgi网络处的分选受体，然后出芽和颗粒形成。我们已经确定了这样的分选受体膜相关羧肽酶E（CPE）在垂体高尔基体丰富的分泌颗粒膜。CPE特异性结合受调节的分泌途径蛋白，包括激素原，但不结合组成型分泌蛋白。我们发现，在CPE（脂肪）突变小鼠缺乏CPE，垂体激素原，前阿黑皮素，是错误的组成途径和分泌的不受管制的方式。因此，CPE（分选受体）的消失导致这些遗传缺陷小鼠的多种内分泌紊乱，包括高胰岛素原血症和不育症。
A proposed mechanism for sorting secretory proteins into granules for release via the regulated secretory pathway in endocrine-neuroendocrine cells involves binding the proteins to a sorting receptor at the transGolgi network, followed by budding and granule formation. We have identified such a sorting receptor as membrane-associated carboxypeptidase E (CPE) in pituitary Golgi-enriched and secretory granule membranes. CPE specifically bound regulated secretory pathway proteins, including prohormones, but not constitutively secreted proteins. We show that in the Cpe(fat) mutant mouse lacking CPE, the pituitary prohormone, pro-opiomelanocortin, was missorted to the constitutive pathway and secreted in an unregulated manner. Thus, obliteration of CPE, the sorting receptor, leads to multiple endocrine disorders in these genetically defective mice, including hyperproinsulinemia and infertility.