Substrate-induced nuclear export and peripheral compartmentalization of hepatic glucokinase correlates with glycogen deposition.
Substrate-induced nuclear export and peripheral compartmentalization of hepatic glucokinase correlates with glycogen deposition.
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DOI：
10.1155/edr.2001.173
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发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Magnuson, M A
中科院分区：
文献类型：
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作者：
Jetton, T L;Shiota, M;Magnuson, M A
肝葡萄糖激酶（GK）通过与其核锚定调节蛋白（GKRP）结合而受到急性调节。虽然GKRP释放的GK与糖原合成的速率紧密相关，但这种关联的性质尚不清楚。为了深入了解生理刺激条件下大鼠肝细胞的这种耦合机制，我们利用共聚焦显微镜和定量图像分析，用免疫荧光分析了GK和GKRP的亚细胞分布，用糖原细胞化学荧光分析了糖原沉积。刺激后，一部分GK信号从细胞核转移到细胞质。核输出指标GK的核与细胞质比值的降低与糖原细胞化学荧光在60分钟刺激期间增加50%相关。此外，糖原积累最初在肝细胞中以类似于GK的外周模式沉积。这些数据表明，活性GK和肝细胞表面糖原沉积的初始位点都存在区隔化。
Hepatic glucokinase (GK) is acutely regulated by binding to its nuclear-anchored regulatory protein (GKRP). Although GK release by GKRP is tightly coupled to the rate of glycogen synthesis, the nature of this association is obscure. To gain insight into this coupling mechanism under physiological stimulating conditions in primary rat hepatocytes, we analyzed the subcellular distribution of GK and GKRP with immunofluorescence, and glycogen deposition with glycogen cytochemical fluorescence, using confocal microscopy and quantitative image analysis. Following stimulation, a fraction of the GK signal translocated from the nucleus to the cytoplasm. The reduction in the nuclear to cytoplasmic ratio of GK, an index of nuclear export, correlated with a >50% increase in glycogen cytochemical fluorescence over a 60 min stimulation period. Furthermore, glycogen accumulation was initially deposited in a peripheral pattern in hepatocytes similar to that of GK. These data suggest that a compartmentalization exists of both active GK and the initial sites of glycogen deposition at the hepatocyte surface.