Abstract：
The Cu(+) pump ATP7B plays an irreplaceable role in the elimination of excess Cu(+) by the hepatocyte into the bile. The trafficking and site of action of ATP7B are subjects of controversy. One current proposal is that an increase in intracellular Cu(+) results in the translocation of ATP7B to the lysosomes and excretion of excess Cu(+) through lysosomal-mediated exocytosis at the bile canaliculus. Here, we show that ATP7B is transported from the trans-Golgi network (TGN) to the bile canaliculus by basolateral sorting and endocytosis, and microtubule-mediated transcytosis through the subapical compartment. Trafficking ATP7B is not incorporated into lysosomes, and addition of Cu(+) does not cause relocalization of lysosomes and the appearance of lysosome markers in the bile canaliculus. Our data reveal the pathway of the Cu(+)-mediated transport of ATP7B from the TGN to the bile canaliculus and indicates that the bile canaliculus is the primary site of ATP7B action in the elimination of excess Cu(.)
摘要：
Cu(+)泵ATP7B在肝细胞清除过量Cu(+)进入胆汁中起着不可替代的作用。ATP7B的贩运和行动地点是有争议的主题。目前的一个建议是，细胞内Cu（）的增加导致ATP7B易位到溶酶体，并通过溶酶体介导的胆汁小管胞吐作用排泄过量的Cu（）。这里,我们显示ATP7B通过基底外侧分选和内吞作用从跨高尔基网络（TGN）运输到胆管，和微管介导的通过根尖下隔室的胞吞作用。贩运ATP7B没有纳入溶酶体，添加Cu（）不会引起溶酶体的重新定位和胆小管中溶酶体标记的出现。我们的数据揭示了Cu（）介导的ATP7B从TGN转运到胆小管的途径，并表明胆小管是消除过量Cu的ATP7B作用的主要部位（。)
