Localization of the Wilson disease protein in murine intestine.

Wilson disease is an inherited disorder of human copper metabolism, characterized by gradual accumulation of copper in tissues, predominantly liver and brain. The gene defect lies in the Wilson disease protein ATP7B, a copper transporting ATPase highly active in hepatocytes. In the liver, ATP7B is essential for excretion of excess copper into the bile and for copper loading of ceruloplasmin in the Golgi apparatus. The extrahepatic role of ATP7B is not yet completely understood. We analysed the intestinal expression of ATP7B in mice using RT-PCR, Western blot and indirect immunofluorescence. We found abundant expression of ATP7B in stomach and small intestine, but not in colon. Using confocal microscopy we demonstrate a Golgi localization of ATP7B in enterocytes. In response to elevated copper, the Wilson disease protein shows an intracellular trafficking pattern in the intestinal polarized cell line CaCo-2, moving away from the Golgi apparatus to dispersed vesicles. This suggests a role for intestinal ATP7B in sequestration of copper in intracellular vesicles for maintenance of copper homeostasis in the enterocyte. In conclusion, the expression of ATP7B in the small intestine might represent an additional regulatory mechanism to fine-tune intestinal copper absorption.