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However, the mechanism of motor neuron degeneration caused by ALS\u2010linked SOD1 mutants is not fully understood. Here, we used novel live cell imaging techniques to demonstrate the subcellular localization of EGFP\u2010fused SOD1 of both wild\u2010type (WT) and ALS\u2010linked mutant forms in the endoplasmic reticulum (ER) and Golgi. The presence of WT and mutant SOD1 species in luminal structures was further confirmed by immunoblotting analysis of microsomal fractions from spinal cord lysates of SOD1 transgenic mice prepared by sucrose density\u2010gradient ultracentrifugation. Chemical cross\u2010linking studies also revealed an age\u2010dependent aggregation of mutant SOD1, but not of WT SOD1, prominently in the microsomal fraction. Cell\u2010free translocation assays provided evidence that monomeric SOD1 is a molecular form that can be translocated into luminal structures in the presence of ATP. Our finding that the ER\u2010Golgi pathway is a predominant cellular site of aggregation of mutant SOD1 suggests that secretion could play a key role in pathogenesis, which is in line with the view that the disease is non\u2010cell autonomous.\u2014Urushitani, M., Ezzi, S. A., Matsuo, A., Tooyama, I., Julien, J.\u2010P. The endoplasmic reticulum\u2010Golgi pathway is a target for translocation and aggregation of mutant superoxide dismutase linked to ALS.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    22, 2476\u20132487 (2008)\n                  <\/jats:p>","DOI":"10.1096\/fj.07-092783","type":"journal-article","created":{"date-parts":[[2008,3,12]],"date-time":"2008-03-12T20:59:30Z","timestamp":1205355570000},"page":"2476-2487","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["The endoplasmic reticulum\u2010Golgi pathway is a target for translocation and aggregation of mutant superoxide dismutase linked to ALS"],"prefix":"10.1096","volume":"22","author":[{"given":"Makoto","family":"Urushitani","sequence":"first","affiliation":[{"name":"Research Centre of Centre Hospitallier Universit\u00e9 de Qu\u00e9bec (CHUQ) Department of Anatomy and Physiology Laval University Laurier Qu\u00e9bec Canada"},{"name":"Molecular Neuroscience Research Center Shiga University of Medical Science Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samer Abou","family":"Ezzi","sequence":"additional","affiliation":[{"name":"Research Centre of Centre Hospitallier Universit\u00e9 de Qu\u00e9bec (CHUQ) Department of Anatomy and Physiology Laval University Laurier Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Molecular Neuroscience Research Center Shiga University of Medical Science Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Tooyama","sequence":"additional","affiliation":[{"name":"Molecular Neuroscience Research Center Shiga University of Medical Science Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Julien","sequence":"additional","affiliation":[{"name":"Research Centre of Centre Hospitallier Universit\u00e9 de Qu\u00e9bec (CHUQ) Department of Anatomy and Physiology Laval University Laurier Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,3,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/362059a0"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/35097565"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00244-6"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.27.070203.144244"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1971"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5248.515"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5449.2498"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/14660820050515160"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.220417997"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010759200"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01211.x"},{"key":"e_1_2_5_13_1","first-page":"7148","article-title":"Disulfide cross-linked protein represents a signifi cant fraction of ALS-associated Cu, Zn-superoxide dismutase aggregates in spinal cords of model mice","volume":"280","author":"Furukawa Y.","year":"2005","journal-title":"Proc. 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