{Reference Type}: Journal Article
{Title}: Basolateral sorting and transcytosis define the Cu+-regulated translocation of ATP7B to the bile canaliculus.
{Author}: Lalioti V;Peiró R;Pérez-Berlanga M;Tsuchiya Y;Muñoz A;Villalba T;Sanchez C;Sandoval IV;
{Journal}: J Cell Sci
{Volume}: 129
{Issue}: 11
{Year}: 06 2016 1
{Factor}: 5.235
{DOI}: 10.1242/jcs.184663
{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(.)