二硫苏糖醇
分泌物
分泌蛋白
分泌途径
嗜铬粒蛋白A
蛋白质水解
胰岛素原
细胞生物学
蛋白质二硫键异构酶
化学
生物化学
生物
二硫键
内质网
胰岛素
内分泌学
高尔基体
酶
免疫学
免疫组织化学
作者
Sven Ulrik Gorr,Xue Fen Huang,Darrin J. Cowley,Regina Kuliawat,Peter Arvan
出处
期刊:American Journal of Physiology-cell Physiology
[American Physiological Society]
日期:1999-07-01
卷期号:277 (1): C121-C131
被引量:64
标识
DOI:10.1152/ajpcell.1999.277.1.c121
摘要
For several secretory proteins, it has been hypothesized that disulfide-bonded loop structures are required for sorting to secretory granules. To explore this hypothesis, we employed dithiothreitol (DTT) treatment in live pancreatic islets, as well as in PC-12 and GH(4)C(1) cells. In islets, disulfide reduction in the distal secretory pathway did not increase constitutive or constitutive-like secretion of proinsulin (or insulin). In PC-12 cells, DTT treatment caused a dramatic increase in unstimulated secretion of newly synthesized chromogranin B (CgB), presumably as a consequence of reducing the single conserved chromogranin disulfide bond (E. Chanat, U. Weiss, W. B. Huttner, and S. A. Tooze. EMBO J. 12: 2159-2168, 1993). However, in GH(4)C(1) cells that also synthesize CgB endogenously, DTT treatment reduced newly synthesized prolactin and blocked its export, whereas newly synthesized CgB was routed normally to secretory granules. Moreover, on transient expression in GH(4)C(1) cells, CgA and a CgA mutant lacking the conserved disulfide bond showed comparable multimeric aggregation properties and targeting to secretory granules, as measured by stimulated secretion assays. Thus the conformational perturbation of regulated secretory proteins caused by disulfide disruption leads to consequences in protein trafficking that are both protein and cell type dependent.
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