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In this study, we found that the expression of mutant\u2010PS1 in stable transfectants of SH\u2010SY5Y neuroblastoma cells results in a reduction of the biosynthesis and steady\u2010state levels of glucosylceramide. As an\n                    <jats:italic>in vivo<\/jats:italic>\n                    corroboration of these data, there was a significant reduction of brain glucosylceramide and gangliosides in an animal model of FAD. In mutant\u2010PS1\u2010transfectants (\n                    <jats:italic>I143T, G384A<\/jats:italic>\n                    ), immunocytochemistry disclosed a remarkable reduction of glucosylceramide synthase (GlcT\u20101)\u2010like immunoreactivity in the cells when compared with those of mock\u2010 and wild\u2010PS1 transfectants. Immunoprecipitation of GlcT\u20101 protein from mutant\u2010PS1 transfectants demonstrated a marked reduction in GlcT\u20101 protein, but there was no reduction in the levels of\n                    <jats:italic>GlcT\u20101<\/jats:italic>\n                    mRNA. Both coprecipitation and \u03b3\u2010secretase inhibition experiments suggest that mutant\u2010PS1 seems to form a complex with GlcT\u20101 protein and to be involved in GlcT\u20101 degradation, which was never found in other cell types. Thus, mutations in the\n                    <jats:italic>PS1<\/jats:italic>\n                    gene result in profound glycosphingolipids abnormalities by abnormal molecular interaction with GlcT\u20101.\u2014Mutoh, T., Kawamura, N., Hirabaysshi, Y., Shima, S., Miyashita, T., Ito, S., Asakura, K., Araki, W., Cazzaniga, E., Muto, E., Masserini, M. Abnormal cross\u2010talk between mutant presenilin 1 (\n                    <jats:italic>I143T, G384A<\/jats:italic>\n                    ) and glycosphingolipid biosynthesis.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 3065\u20133074 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-198630","type":"journal-article","created":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T01:46:10Z","timestamp":1334627170000},"page":"3065-3074","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Abnormal cross\u2010talk between mutant presenilin 1 (\n                    <i>I143T, G384A<\/i>\n                    ) and glycosphingolipid biosynthesis"],"prefix":"10.1096","volume":"26","author":[{"given":"Tatsuro","family":"Mutoh","sequence":"first","affiliation":[{"name":"Department of Neurology Fujita Health University School of Medicine  Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Neurology Fujita Health University School of Medicine  Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Hirabayashi","sequence":"additional","affiliation":[{"name":"Neuronal Circuit Mechanism Research Group Brain Science Institute, RIKEN  Wako Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayuri","family":"Shima","sequence":"additional","affiliation":[{"name":"Department of Neurology Fujita Health University School of Medicine  Toyoake 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