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In contrast to a mutation designed to prevent adenosine triphosphate (ATP) binding, an ATP hydrolysis\u2013deficient Spastin mutant predicted to remain kinetically trapped on target proteins decorates microtubules in transfected cells. Analysis of disease-associated missense mutations shows that some more closely resemble the canonical hydrolysis mutant, whereas others resemble the ATP-binding mutant. Using real-time imaging, we show that Spastin severs microtubules when added to permeabilized, cytosol-depleted cells stably expressing GFP-tubulin. Using purified components, we also show that Spastin interacts directly with microtubules and is sufficient for severing. These studies suggest that defects in microtubule severing are a cause of axonal degeneration in human disease.<\/jats:p>","DOI":"10.1083\/jcb.200409058","type":"journal-article","created":{"date-parts":[[2005,2,16]],"date-time":"2005-02-16T13:03:22Z","timestamp":1108559002000},"page":"599-606","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":194,"title":["Linking axonal degeneration to microtubule remodeling by Spastin-mediated microtubule severing"],"prefix":"10.1083","volume":"168","author":[{"given":"Katia J.","family":"Evans","sequence":"first","affiliation":[{"name":"1Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032"},{"name":"2Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032"}]},{"given":"Edgar R.","family":"Gomes","sequence":"additional","affiliation":[{"name":"1Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032"},{"name":"3Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032"}]},{"given":"Steven M.","family":"Reisenweber","sequence":"additional","affiliation":[{"name":"1Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032"},{"name":"2Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032"}]},{"given":"Gregg G.","family":"Gundersen","sequence":"additional","affiliation":[{"name":"1Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032"},{"name":"3Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032"}]},{"given":"Brett P.","family":"Lauring","sequence":"additional","affiliation":[{"name":"1Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032"},{"name":"2Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032"}]}],"member":"291","published-online":{"date-parts":[[2005,2,14]]},"reference":[{"key":"2023072218475113000_BIB1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1083\/jcb.145.2.305","volume":"145","year":"1999","journal-title":"J. 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