Functional Studies on the Wilson Copper P-Type ATPase and Toxic Milk Mouse Mutant
The Wilson protein (WND; ATP7B) is an essential component of copper homeostasis. Mutations in the ATP7B gene result in Wilson disease, which is characterised by hepatotoxicity and neurological disturbances. In this paper, we provide the first direct biochemical evidence that the WND protein function...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2001-03, Vol.281 (4), p.966-970 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Voskoboinik, I. Greenough, M. La Fontaine, S. Mercer, J.F.B. Camakaris, J. |
| description | The Wilson protein (WND; ATP7B) is an essential component of copper homeostasis. Mutations in the ATP7B gene result in Wilson disease, which is characterised by hepatotoxicity and neurological disturbances. In this paper, we provide the first direct biochemical evidence that the WND protein functions as a copper-translocating P-type ATPase in mammalian cells. Importantly, we have shown that the mutation of the conserved Met1386 to Val, in the Atp7B for the mouse model of Wilson disease, toxic milk (tx), caused a loss of Cu-translocating activity. These investigations provide strong evidence that the toxic milk mouse is a valid model for Wilson disease and demonstrate a link between the loss of catalytic function of WND and the Wilson disease phenotype. |
| doi_str_mv | 10.1006/bbrc.2001.4445 |
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Mutations in the ATP7B gene result in Wilson disease, which is characterised by hepatotoxicity and neurological disturbances. In this paper, we provide the first direct biochemical evidence that the WND protein functions as a copper-translocating P-type ATPase in mammalian cells. Importantly, we have shown that the mutation of the conserved Met1386 to Val, in the Atp7B for the mouse model of Wilson disease, toxic milk (tx), caused a loss of Cu-translocating activity. 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Mutations in the ATP7B gene result in Wilson disease, which is characterised by hepatotoxicity and neurological disturbances. In this paper, we provide the first direct biochemical evidence that the WND protein functions as a copper-translocating P-type ATPase in mammalian cells. Importantly, we have shown that the mutation of the conserved Met1386 to Val, in the Atp7B for the mouse model of Wilson disease, toxic milk (tx), caused a loss of Cu-translocating activity. These investigations provide strong evidence that the toxic milk mouse is a valid model for Wilson disease and demonstrate a link between the loss of catalytic function of WND and the Wilson disease phenotype.</description><subject>Adenosine Triphosphatases - genetics</subject><subject>Adenosine Triphosphatases - metabolism</subject><subject>Animals</subject><subject>ATP7B gene</subject><subject>Biological Transport - drug effects</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cation Transport Proteins</subject><subject>CHO Cells</subject><subject>copper</subject><subject>Copper - metabolism</subject><subject>Copper-transporting ATPases</subject><subject>Cricetinae</subject><subject>DNA, Recombinant - genetics</subject><subject>heavy metals</subject><subject>Kinetics</subject><subject>Membranes - drug effects</subject><subject>Membranes - metabolism</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>Mutation</subject><subject>P-type ATPase</subject><subject>Time Factors</subject><subject>toxic milk mouse</subject><subject>Transfection</subject><subject>Transport Vesicles - drug effects</subject><subject>Transport Vesicles - metabolism</subject><subject>Vanadates - pharmacology</subject><subject>Wilson disease</subject><subject>Wilson protein</subject><subject>WND protein</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1LAzEQhoMotlavHiUnb1snm_08lmJVaLFiRW8hH1OMbnfXZFfsvzelBU-eZhieeZl5CLlkMGYA2Y1STo9jADZOkiQ9IkMGJUQxg-SYDCEQUVyytwE58_4jUCzJylMyYCzmeZ5mQ_I062vd2aaWFX3uemPR06am3TvSV1v50E6btkVHl9Fq2yKdrJbSI5W1oavmx2q6sNUnXTR9GC76TtbdOTlZy8rjxaGOyMvsdjW9j-aPdw_TyTzSPGddlEkseM5BQ1wqUyTA1zEvFRRaqTLNjIJEgtKFNolK85QZhphl0qS8WBcMOB-R631u65qvHn0nNtZrrCpZYzhHsLxgWVqWARzvQe0a7x2uRevsRrqtYCB2EsVOothJFDuJYeHqkNyrDZo__GAtAMUewPDft0UnvLZYazTWoe6Eaex_2b-JmH9n</recordid><startdate>20010309</startdate><enddate>20010309</enddate><creator>Voskoboinik, I.</creator><creator>Greenough, M.</creator><creator>La Fontaine, S.</creator><creator>Mercer, J.F.B.</creator><creator>Camakaris, J.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20010309</creationdate><title>Functional Studies on the Wilson Copper P-Type ATPase and Toxic Milk Mouse Mutant</title><author>Voskoboinik, I. ; Greenough, M. ; La Fontaine, S. ; Mercer, J.F.B. ; Camakaris, J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-6ae83730c029bd8403f239b08cbb956db04a0bc8cd4b5751d1ee66ad538f81033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adenosine Triphosphatases - genetics</topic><topic>Adenosine Triphosphatases - metabolism</topic><topic>Animals</topic><topic>ATP7B gene</topic><topic>Biological Transport - drug effects</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cation Transport Proteins</topic><topic>CHO Cells</topic><topic>copper</topic><topic>Copper - metabolism</topic><topic>Copper-transporting ATPases</topic><topic>Cricetinae</topic><topic>DNA, Recombinant - genetics</topic><topic>heavy metals</topic><topic>Kinetics</topic><topic>Membranes - drug effects</topic><topic>Membranes - metabolism</topic><topic>Mice</topic><topic>Mice, Mutant Strains</topic><topic>Mutation</topic><topic>P-type ATPase</topic><topic>Time Factors</topic><topic>toxic milk mouse</topic><topic>Transfection</topic><topic>Transport Vesicles - drug effects</topic><topic>Transport Vesicles - metabolism</topic><topic>Vanadates - pharmacology</topic><topic>Wilson disease</topic><topic>Wilson protein</topic><topic>WND protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Voskoboinik, I.</creatorcontrib><creatorcontrib>Greenough, M.</creatorcontrib><creatorcontrib>La Fontaine, S.</creatorcontrib><creatorcontrib>Mercer, J.F.B.</creatorcontrib><creatorcontrib>Camakaris, J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Voskoboinik, I.</au><au>Greenough, M.</au><au>La Fontaine, S.</au><au>Mercer, J.F.B.</au><au>Camakaris, J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional Studies on the Wilson Copper P-Type ATPase and Toxic Milk Mouse Mutant</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2001-03-09</date><risdate>2001</risdate><volume>281</volume><issue>4</issue><spage>966</spage><epage>970</epage><pages>966-970</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>The Wilson protein (WND; ATP7B) is an essential component of copper homeostasis. Mutations in the ATP7B gene result in Wilson disease, which is characterised by hepatotoxicity and neurological disturbances. In this paper, we provide the first direct biochemical evidence that the WND protein functions as a copper-translocating P-type ATPase in mammalian cells. Importantly, we have shown that the mutation of the conserved Met1386 to Val, in the Atp7B for the mouse model of Wilson disease, toxic milk (tx), caused a loss of Cu-translocating activity. These investigations provide strong evidence that the toxic milk mouse is a valid model for Wilson disease and demonstrate a link between the loss of catalytic function of WND and the Wilson disease phenotype.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11237756</pmid><doi>10.1006/bbrc.2001.4445</doi><tpages>5</tpages></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adenosine Triphosphatases - genetics Adenosine Triphosphatases - metabolism Animals ATP7B gene Biological Transport - drug effects Carrier Proteins - genetics Carrier Proteins - metabolism Cation Transport Proteins CHO Cells copper Copper - metabolism Copper-transporting ATPases Cricetinae DNA, Recombinant - genetics heavy metals Kinetics Membranes - drug effects Membranes - metabolism Mice Mice, Mutant Strains Mutation P-type ATPase Time Factors toxic milk mouse Transfection Transport Vesicles - drug effects Transport Vesicles - metabolism Vanadates - pharmacology Wilson disease Wilson protein WND protein |
| title | Functional Studies on the Wilson Copper P-Type ATPase and Toxic Milk Mouse Mutant |
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