Basolateral sorting and transcytosis define the cu+-regulated translocation of ATP7B to the bile canaliculus
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...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/150712 |
| Acceso en línea: | http://hdl.handle.net/10261/150712 |
| Access Level: | acceso abierto |
| Palabra clave: | Copper Trafficking TGN Bile canaliculus Transcytosis ATP7B |
| Sumario: | 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. |
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