%0 Journal Article
%T Basolateral sorting and transcytosis define the Cu+-regulated translocation of ATP7B to the bile canaliculus.
%A Lalioti V
%A Peiró R
%A Pérez-Berlanga M
%A Tsuchiya Y
%A Muñoz A
%A Villalba T
%A Sanchez C
%A Sandoval IV
%J J Cell Sci
%V 129
%N 11
%D 06 2016 1
%M 27034138
%F 5.235
%R 10.1242/jcs.184663
%X 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(.)