{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T16:38:01Z","timestamp":1791131881272,"version":"4.1.0"},"reference-count":26,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5613","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2003,3,14]]},"abstract":"<jats:p>\n                    Mutations in proteins of the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    phototransduction cascade, a prototypic guanine nucleotide\u2013binding protein\u2013coupled receptor signaling system, lead to retinal degeneration and have been used as models to understand human degenerative disorders. Here, modulating the sphingolipid biosynthetic pathway rescued retinal degeneration in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    mutants. Targeted expression of\n                    <jats:italic>Drosophila<\/jats:italic>\n                    neutral ceramidase rescued retinal degeneration in arrestin and phospholipase C mutants. Decreasing flux through the de novo sphingolipid biosynthetic pathway also suppressed degeneration in these mutants. Both genetic backgrounds modulated the endocytic machinery because they suppressed defects in a dynamin mutant. Suppression of degeneration in arrestin mutant flies expressing ceramidase correlated with a decrease in ceramide levels. Thus, enzymes of sphingolipid metabolism may be suitable targets in the therapeutic management of retinal degeneration.\n                  <\/jats:p>","DOI":"10.1126\/science.1080549","type":"journal-article","created":{"date-parts":[[2003,3,13]],"date-time":"2003-03-13T16:43:18Z","timestamp":1047573798000},"page":"1740-1743","source":"Crossref","is-referenced-by-count":116,"title":["Modulating Sphingolipid Biosynthetic Pathway Rescues Photoreceptor Degeneration"],"prefix":"10.1126","volume":"299","author":[{"given":"Usha","family":"Acharya","sequence":"first","affiliation":[{"name":"Regulation of Cell Growth Laboratory, National Cancer Institute\u2013Frederick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shetal","family":"Patel","sequence":"additional","affiliation":[{"name":"Regulation of Cell Growth Laboratory, National Cancer Institute\u2013Frederick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund","family":"Koundakjian","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunio","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Electron Microscopy Facility\/Image Analysis Laboratory, Science Applications International Corporation, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlin","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Bioorganic Chemistry and Molecular Pharmacology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jairaj K.","family":"Acharya","sequence":"additional","affiliation":[{"name":"Regulation of Cell Growth Laboratory, National Cancer Institute\u2013Frederick, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi002836k"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(02)02277-8"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(00)11081-X"},{"key":"e_1_3_1_5_2","unstructured":"K. D'Hondt"},{"key":"e_1_3_1_5_3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.34.1.255"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.07.110191.001113"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.15.1.231"},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","unstructured":"J. E. O'Tousa in Progress in Retinal Eye Research N. N. Osbourne G. J. Chader Eds. (Elsevier New York 1997) p. 691.","DOI":"10.1016\/S1350-9462(96)00035-3"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8316831"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(00)00190-3"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00092-1"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00091-X"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.118.2.401"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81385-9"},{"key":"e_1_3_1_15_2","unstructured":"Materials and methods are available as supporting material on Science Online."},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2001.5536"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.10.7276"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.16.1.483"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0854.2000.010503.x"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(90)90212-2"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/35078077"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6989(01)00229-2"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.10-08-02749.1990"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(01)00023-5"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1076\/opge.22.3.133.2224"},{"key":"e_1_3_1_26_2","unstructured":"We thank C. Zuker T. Kitamoto and the Drosophila stock center (Bloomington Indiana) for fly stocks; M. Mowen and K. Stanard for technical assistance; and C. Zuker V. Malhotra M. Fortini I. Daar and A. Weissman for comments on the manuscript."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1080549","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:42:39Z","timestamp":1704836559000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1080549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,3,14]]},"references-count":26,"journal-issue":{"issue":"5613","published-print":{"date-parts":[[2003,3,14]]}},"alternative-id":["10.1126\/science.1080549"],"URL":"https:\/\/doi.org\/10.1126\/science.1080549","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1010564.186072","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1010564.187812","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,3,14]]}}}