Copper exposure induces trafficking of the Menkes protein in intestinal epithelium of ATP7A transgenic mice
Copper exposure induces trafficking of the Menkes protein in intestinal epithelium of ATP7A transgenic mice
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DOI：
10.1093/jn/135.12.2762
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发表时间：
2005-12-01
影响因子：
4.2
通讯作者：
Kramer, DR
中科院分区：
文献类型：
--
作者：
Monty, JF;Llanos, RM;Kramer, DR
在分子水平上铜的吸收和排泄的最后步骤是由两种密切相关的蛋白质完成的，它们催化依赖于ATP的铜通过质膜的运输。这些蛋白质，ATP7A和ATP7B，是由人类遗传性铜运输障碍，即门克斯和威尔逊病所影响的基因编码的。用冰冻切片免疫荧光法研究了ATP7A转基因小鼠空肠离体铜灌流对ATP7A细胞内分布的影响。我们的结果表明，在铜限制的条件下，ATP7A被保留在跨高尔基体网络中，但在灌铜的肠道中，ATP7A被重新定位到靠近基底膜的囊泡室。这些发现支持这样一种假设，即铜从肠细胞到门脉血液的基侧运输可能涉及ATP7A将铜泵入囊腔，然后胞吐释放铜，而不是直接将铜泵入基侧膜。
The final steps in the absorption and excretion of copper at the molecular level are accomplished by 2 closely related proteins that catalyze the ATP-dependent transport of copper across the plasma membrane. These proteins, ATP7A and ATP7B, are encoded by the genes affected in human genetic copper-transport disorders, namely, Menkes and Wilson diseases. We studied the effect of copper perfusion of an isolated segment of the jejunum of ATP7A transgenic mice on the intracellular distribution of ATP7A by immunofluorescence of frozen sections. Our results indicate that ATP7A is retained in the trans-Golgi network under copper-limiting conditions, but relocalized to a vesicular compartment adjacent to the basolateral membrane in intestines perfused with copper. The findings support the hypothesis that the basolateral transport of copper from the enterocyte into the portal blood may involve ATP7A pumping copper into a vesicular compartment followed by exocytosis to release the copper, rather than direct pumping of copper across the basolateral membrane.