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Surprisingly, ATP-bound torsinA is recruited to the nuclear envelope (NE) of transfected cells, where it alters connections between inner and outer nuclear membranes. In contrast, ATP-free torsinA is diffusely distributed throughout the endoplasmic reticulum and has no effect on the NE. Among AAA+ ATPases, affinity for substrates is high in the ATP-bound and low in the ATP-free state, leading us to propose that component(s) of the NE may be substrates for torsinA. We also find that the disease-promoting \u0394E302\/303 mutant is in the NE, and that this relocalization, as well as the mutant's previously described ability to induce membranous inclusions, is eliminated by the K108A ATP-binding mutation. These results suggest that changes in interactions involving torsinA in the NE could be important for the pathogenesis of dystonia and point to torsinA and related proteins as a class of ATPases that may operate in the NE.<\/jats:p>","DOI":"10.1073\/pnas.0308760101","type":"journal-article","created":{"date-parts":[[2004,5,10]],"date-time":"2004-05-10T21:04:10Z","timestamp":1084223050000},"page":"7612-7617","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":212,"title":["TorsinA in the nuclear envelope"],"prefix":"10.1073","volume":"101","author":[{"given":"Teresa V.","family":"Naismith","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110; and Departments of Neurology and Radiology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Heuser","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110; and Departments of Neurology and Radiology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xandra O.","family":"Breakefield","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110; and Departments of Neurology and Radiology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phyllis I.","family":"Hanson","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110; and Departments of Neurology and Radiology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,5,10]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"1","volume":"78","year":"1998","unstructured":"Fahn, S., Bressman, S. 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