{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:06:57Z","timestamp":1791396417226,"version":"4.3.3"},"reference-count":38,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,2,27]]},"abstract":"<jats:p>The microtubule motor cytoplasmic dynein and its activator dynactin drive vesicular transport and mitotic spindle organization. Dynactin is ubiquitously expressed in eukaryotes, but a G59S mutation in the p150Glued subunit of dynactin results in the specific degeneration of motor neurons. This mutation in the conserved cytoskeleton-associated protein, glycine-rich (CAP-Gly) domain lowers the affinity of p150Glued for microtubules and EB1. Cell lines from patients are morphologically normal but show delayed recovery after nocodazole treatment, consistent with a subtle disruption of dynein\/dynactin function. The G59S mutation disrupts the folding of the CAP-Gly domain, resulting in aggregation of the p150Glued protein both in vitro and in vivo, which is accompanied by an increase in cell death in a motor neuron cell line. Overexpression of the chaperone Hsp70 inhibits aggregate formation and prevents cell death. These data support a model in which a point mutation in p150Glued causes both loss of dynein\/dynactin function and gain of toxic function, which together lead to motor neuron cell death.<\/jats:p>","DOI":"10.1083\/jcb.200511068","type":"journal-article","created":{"date-parts":[[2006,2,27]],"date-time":"2006-02-27T15:53:19Z","timestamp":1141055599000},"page":"733-745","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":169,"title":["A motor neuron disease\u2013associated mutation in p150Glued perturbs dynactin function and induces protein aggregation"],"prefix":"10.1083","volume":"172","author":[{"given":"Jennifer R.","family":"Levy","sequence":"first","affiliation":[{"name":"1Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte J.","family":"Sumner","sequence":"additional","affiliation":[{"name":"2Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane P.","family":"Caviston","sequence":"additional","affiliation":[{"name":"1Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko K.","family":"Tokito","sequence":"additional","affiliation":[{"name":"1Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srikanth","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"2Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee A.","family":"Ligon","sequence":"additional","affiliation":[{"name":"1Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E.","family":"Wallace","sequence":"additional","affiliation":[{"name":"1Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette H.","family":"LaMonte","sequence":"additional","affiliation":[{"name":"1Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George G.","family":"Harmison","sequence":"additional","affiliation":[{"name":"2Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imke","family":"Puls","sequence":"additional","affiliation":[{"name":"2Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth H.","family":"Fischbeck","sequence":"additional","affiliation":[{"name":"2Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika L.F.","family":"Holzbaur","sequence":"additional","affiliation":[{"name":"1Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2006,2,27]]},"reference":[{"key":"2023072909592607100_BIB1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.semcdb.2003.12.010","volume":"15","year":"2004","journal-title":"Semin. 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