PROTEOLYTIC MATURATION OF INSULIN IS A POST-GOLGI EVENT WHICH OCCURS IN ACIDIFYING CLATHRIN-COATED SECRETORY VESICLES
PROTEOLYTIC MATURATION OF INSULIN IS A POST-GOLGI EVENT WHICH OCCURS IN ACIDIFYING CLATHRIN-COATED SECRETORY VESICLES
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DOI：
10.1016/0092-8674(87)90624-6
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发表时间：
1987-06-19
期刊：
影响因子：
64.5
通讯作者：
PERRELET, A
中科院分区：
文献类型：
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作者：
ORCI, L;RAVAZZOLA, M;PERRELET, A
使用胰岛素特异性单克隆抗体通过免疫细胞化学直接鉴定胰岛素原蛋白水解加工成胰岛素的细胞内位点。胰腺 B 细胞的高尔基体堆栈中不存在胰岛素免疫反应性，并且首先在从跨高尔基体极释放的网格蛋白包被的分泌囊泡中可检测到。网格蛋白包被的分泌小泡转变成成熟的非包被的分泌颗粒，其中含有最高浓度的胰岛素免疫反应位点。网格蛋白包被的分泌囊泡的成熟伴随着囊泡环境的逐渐酸化，这一点可以通过在酸性区室中积累的细胞化学探针来证明，随后可以通过免疫细胞化学来揭示。因此，激素原在分泌囊泡中的包装以及该区室的酸化是胰岛素适当蛋白水解成熟的关键步骤。
The direct identification of the intracellular site where proinsulin is proteolytically processed into insulin has been achieved by immunocytochemistry using an insulin-specific monoclonal antibody. Insulin immunoreactivity is absent from the Golgi stack of pancreatic B-cells and first becomes detectable in clathrin-coated secretory vesicles released from the trans Golgi pole. Clathrin-coated secretory vesicles transform into mature noncoated secretory granules which contain the highest concentration of insulin immunoreactive sites. Maturation of clathrin-coated secretory vesicles is accompanied by a progressive acidification of the vesicular milieu, as evidenced by a cytochemical probe that accumulates in acidic compartments whereupon it can be revealed by immunocytochemistry. Thus packaging of the prohormone in secretory vesicles, and acidification of this compartment, are critical steps in the proper proteolytic maturation of insulin.