Copper-dependent trafficking of Wilson disease mutant ATP7B proteins

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Copper-dependent trafficking of Wilson disease mutant ATP7B proteins.

We have previously developed a functional assay in yeast for the copper transporter, ATP7B, defective in Wilson disease (WND). Analysis of WND variant ATP7B proteins revealed that several were able to completely, or nearly completely, complement a mutant yeast strain in which the ATP7B ortholog CCC2 was disrupted, indicating that these ATP7B proteins retained copper transport activity. We analy...

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Wilson Disease Protein ATP7B Utilizes Lysosomal Exocytosis to Maintain Copper Homeostasis

Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we show that, in response to elevated copper, ATP7B moves from the Golgi to lysosomes and imports me...

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Novel mutations in ATP7B gene of Wilson\'s disease in Iranian patients

Bacground: Wilson's disease is a rare autosomal recessive disorder characterized by toxic accumulation of copper in liver and brain. The disorder is caused by mutations in the ATP7B gene, encoding a copper transporting P-type ATPase. Characterization of the spectrum of mutations in this gene is important both for diagnosis and genetic counseling of the families. Materials and Methods: We enrol...

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Solution structures of the actuator domain of ATP7A and ATP7B, the Menkes and Wilson disease proteins.

ATP7A and ATP7B are two human P(1B)-type ATPases that have a crucial role in maintaining copper(I) homeostasis. Among the various domains of these enzymes, one, called the Actuator or A-domain, has a regulatory function and is required for the phosphatase step of the catalytic cycle (dephosphorylation of the intermediate formed during ATP hydrolysis). Here we report the solution structures of t...

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Retinal localization and copper-dependent relocalization of the Wilson and Menkes disease proteins.

PURPOSE Menkes and Wilson diseases are associated with retinal degeneration. The Menkes and Wilson genes are homologous copper transporters, but differences in their expression pattern lead to different disease manifestations. To determine whether the Wilson and Menkes genes may act locally in the retina, this study was undertaken to assess retinal Wilson and Menkes expression and localization....

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ژورنال

عنوان ژورنال: Human Molecular Genetics

سال: 2000

ISSN: 1460-2083

DOI: 10.1093/hmg/9.13.1927