Regulation of Torsin ATPases by LAP1 and LULL1
TorsinA is a membrane-associated AAA+ (ATPases associated with a variety of cellular activities) ATPase implicated in primary dystonia, an autosomal-dominant movement disorder. We reconstituted TorsinA and its cofactors in vitro and show that TorsinA does not display ATPase activity in isolation; AT...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2013-04, Vol.110 (17), p.E1545-E1554 |
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| creator | Zhao, Chenguang Brown, Rebecca S H Chase, Anna R Eisele, Markus R Schlieker, Christian |
| description | TorsinA is a membrane-associated AAA+ (ATPases associated with a variety of cellular activities) ATPase implicated in primary dystonia, an autosomal-dominant movement disorder. We reconstituted TorsinA and its cofactors in vitro and show that TorsinA does not display ATPase activity in isolation; ATP hydrolysis is induced upon association with LAP1 and LULL1, type II transmembrane proteins residing in the nuclear envelope and endoplasmic reticulum. This interaction requires TorsinA to be in the ATP-bound state, and can be attributed to the luminal domains of LAP1 and LULL1. This ATPase activator function controls the activities of other members of the Torsin family in distinct fashion, leading to an acceleration of the hydrolysis step by up to two orders of magnitude. The dystonia-causing mutant of TorsinA is defective in this activation mechanism, suggesting a loss-of-function mechanism for this congenital disorder. |
| doi_str_mv | 10.1073/pnas.1300676110 |
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We reconstituted TorsinA and its cofactors in vitro and show that TorsinA does not display ATPase activity in isolation; ATP hydrolysis is induced upon association with LAP1 and LULL1, type II transmembrane proteins residing in the nuclear envelope and endoplasmic reticulum. This interaction requires TorsinA to be in the ATP-bound state, and can be attributed to the luminal domains of LAP1 and LULL1. This ATPase activator function controls the activities of other members of the Torsin family in distinct fashion, leading to an acceleration of the hydrolysis step by up to two orders of magnitude. 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The dystonia-causing mutant of TorsinA is defective in this activation mechanism, suggesting a loss-of-function mechanism for this congenital disorder.</description><subject>Adenosine triphosphatase</subject><subject>Adenosine Triphosphatases - metabolism</subject><subject>adenosine triphosphate</subject><subject>adenosinetriphosphatase</subject><subject>Biological Sciences</subject><subject>Carrier Proteins - metabolism</subject><subject>Chromatography, Gel</subject><subject>Cloning, Molecular</subject><subject>Congenital diseases</subject><subject>Dystonia Musculorum Deformans - genetics</subject><subject>Dystonia Musculorum Deformans - metabolism</subject><subject>endoplasmic reticulum</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>HEK293 Cells</subject><subject>HeLa Cells</subject><subject>HSC70 Heat-Shock Proteins - metabolism</subject><subject>Humans</subject><subject>Hydrolysis</subject><subject>Immunoblotting</subject><subject>Immunoprecipitation</subject><subject>Membrane Proteins - metabolism</subject><subject>Membranes</subject><subject>Molecular Chaperones - genetics</subject><subject>Molecular Chaperones - metabolism</subject><subject>mutants</subject><subject>Mutation</subject><subject>Neurological disorders</subject><subject>nuclear membrane</subject><subject>PNAS Plus</subject><subject>Proteins</subject><subject>transmembrane proteins</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQRi0EokvhzA0iceGS7Ywdx_YFaVUVqBSpVdk9W5PEWVJl48XeVOq_x8suS-HCaQ7z5mlmPsbeIswRlLjYjhTnKABKVSLCMzZDMJiXhYHnbAbAVa4LXpyxVzHeA4CRGl6yMy5kaTgXMza_c-tpoF3vx8x32dKH2I_ZYnlL0cWsfsyqxS1mNLZZtaoqfM1edDRE9-ZYz9nq89Xy8mte3Xy5vlxUeZPEu7wB7Rwo1wgtpahbqp3kxLWQtWiLhrDh0BIVrdBlzbV0piFSRvHaqFJ3tThnnw7e7VRvXNu4cRdosNvQbyg8Wk-9_bsz9t_t2j9YUQqVTkuCj0dB8D8mF3d208fGDQONzk_RogYBRkit_o-KIv1WoTEJ_fAPeu-nMKZP_KIUStQ6URcHqgk-xuC6094Idh-b3cdm_8SWJt49PffE_84pAdkR2E-edHufslcoC5mQ9wekI29pHfpoV984YAmAQqUifgI-rqRV</recordid><startdate>20130423</startdate><enddate>20130423</enddate><creator>Zhao, Chenguang</creator><creator>Brown, Rebecca S H</creator><creator>Chase, Anna R</creator><creator>Eisele, Markus R</creator><creator>Schlieker, Christian</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20130423</creationdate><title>Regulation of Torsin ATPases by LAP1 and LULL1</title><author>Zhao, Chenguang ; Brown, Rebecca S H ; Chase, Anna R ; Eisele, Markus R ; Schlieker, Christian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c569t-c08ee07ec38553bdabe52a2835b3d4ca1c20daa4d386b285e9caa7972b9768fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adenosine triphosphatase</topic><topic>Adenosine Triphosphatases - metabolism</topic><topic>adenosine triphosphate</topic><topic>adenosinetriphosphatase</topic><topic>Biological Sciences</topic><topic>Carrier Proteins - metabolism</topic><topic>Chromatography, Gel</topic><topic>Cloning, Molecular</topic><topic>Congenital diseases</topic><topic>Dystonia Musculorum Deformans - genetics</topic><topic>Dystonia Musculorum Deformans - metabolism</topic><topic>endoplasmic reticulum</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>HEK293 Cells</topic><topic>HeLa Cells</topic><topic>HSC70 Heat-Shock Proteins - metabolism</topic><topic>Humans</topic><topic>Hydrolysis</topic><topic>Immunoblotting</topic><topic>Immunoprecipitation</topic><topic>Membrane Proteins - metabolism</topic><topic>Membranes</topic><topic>Molecular Chaperones - genetics</topic><topic>Molecular Chaperones - metabolism</topic><topic>mutants</topic><topic>Mutation</topic><topic>Neurological disorders</topic><topic>nuclear membrane</topic><topic>PNAS Plus</topic><topic>Proteins</topic><topic>transmembrane proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Chenguang</creatorcontrib><creatorcontrib>Brown, Rebecca S H</creatorcontrib><creatorcontrib>Chase, Anna R</creatorcontrib><creatorcontrib>Eisele, Markus R</creatorcontrib><creatorcontrib>Schlieker, Christian</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Chenguang</au><au>Brown, Rebecca S H</au><au>Chase, Anna R</au><au>Eisele, Markus R</au><au>Schlieker, Christian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of Torsin ATPases by LAP1 and LULL1</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2013-04-23</date><risdate>2013</risdate><volume>110</volume><issue>17</issue><spage>E1545</spage><epage>E1554</epage><pages>E1545-E1554</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>TorsinA is a membrane-associated AAA+ (ATPases associated with a variety of cellular activities) ATPase implicated in primary dystonia, an autosomal-dominant movement disorder. 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| subjects | Adenosine triphosphatase Adenosine Triphosphatases - metabolism adenosine triphosphate adenosinetriphosphatase Biological Sciences Carrier Proteins - metabolism Chromatography, Gel Cloning, Molecular Congenital diseases Dystonia Musculorum Deformans - genetics Dystonia Musculorum Deformans - metabolism endoplasmic reticulum Endoplasmic Reticulum - metabolism HEK293 Cells HeLa Cells HSC70 Heat-Shock Proteins - metabolism Humans Hydrolysis Immunoblotting Immunoprecipitation Membrane Proteins - metabolism Membranes Molecular Chaperones - genetics Molecular Chaperones - metabolism mutants Mutation Neurological disorders nuclear membrane PNAS Plus Proteins transmembrane proteins |
| title | Regulation of Torsin ATPases by LAP1 and LULL1 |
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