Genetic, metabolic and cellular factors influencing intracellular localization of the Wilson disease protein, ATP7B

Background Wilson disease (WD) is a disorder of copper accumulation in liver and brain caused by mutations in the coppertransporting ATPase ATP7B that affects 1 in 5000 live births. Under basal conditions, ATP7B protein localizes to the trans-Golgi network (TGN) but traffics to vesicles in response to high copper. The purpose of the study is to identify genetic, metabolic and regulatory factors that regulate ATP7B function and localization to maintain normal copper homeostasis in cells. The study is divided into three parts, (a) Role of copper in normal protein folding and its ER exit, (b) Role of regulatory phosphorylation of ATP7B in its trafficking from TGN to vesicles (c) Interaction of ATP7B with regulatory proteins in its trafficking route.