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Gain- and loss-of-function analyses show that sphingosine kinases affect trafficking of the G protein\u2013coupled receptor Rhodopsin and the light-sensitive transient receptor potential (TRP) channel by modulating the levels of dihydrosphingosine 1 phosphate (DHS1P) and sphingosine 1 phosphate (S1P). An increase in DHS1P levels relative to S1P leads to the enhanced lysosomal degradation of Rhodopsin and TRP and retinal degeneration in wild-type photoreceptors. Our results suggest that sphingosine kinases and their metabolites modulate photoreceptor homeostasis by influencing endolysosomal trafficking of Rhodopsin and TRP.<\/jats:p>","DOI":"10.1083\/jcb.201004098","type":"journal-article","created":{"date-parts":[[2011,2,15]],"date-time":"2011-02-15T10:18:11Z","timestamp":1297765091000},"page":"557-567","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":39,"title":["Sphingosine kinases and their metabolites modulate endolysosomal trafficking in photoreceptors"],"prefix":"10.1083","volume":"192","author":[{"given":"Ikuko","family":"Yonamine","sequence":"first","affiliation":[{"name":"Program in Gene Function and Expression 1 and 2"},{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605 1 and 2"},{"name":"Program in Gene Function and Expression 1 and 2"},{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Bamba","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niraj K.","family":"Nirala","sequence":"additional","affiliation":[{"name":"Program in Gene Function and Expression 1 and 2"},{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605 1 and 2"},{"name":"Program in Gene Function and Expression 1 and 2"},{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahid","family":"Jesmin","sequence":"additional","affiliation":[{"name":"Program in Gene Function and Expression 1 and 2"},{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605 1 and 2"},{"name":"Program in Gene Function and Expression 1 and 2"},{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Kosakowska-Cholody","sequence":"additional","affiliation":[{"name":"Laboratory of Cell and Developmental Signaling, National Cancer Institute, Frederick, MD 21702 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunio","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Electron Microscopy Facility and Image Analysis Laboratory, Science Applications International Corporation\u2013Frederick, Frederick, MD 21702 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichiro","family":"Fukusaki","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jairaj K.","family":"Acharya","sequence":"additional","affiliation":[{"name":"Laboratory of Cell and Developmental Signaling, National Cancer Institute, Frederick, MD 21702 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usha","family":"Acharya","sequence":"additional","affiliation":[{"name":"Program in Gene Function and Expression 1 and 2"},{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605 1 and 2"},{"name":"Program in Gene Function and Expression 1 and 2"},{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2011,2,14]]},"reference":[{"key":"2023072300521843500_bib1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.neuron.2007.10.041","article-title":"Cell-nonautonomous function of ceramidase in photoreceptor homeostasis","volume":"57","author":"Acharya","year":"2008","journal-title":"Neuron."},{"key":"2023072300521843500_bib2","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1007\/s00018-004-4254-1","article-title":"Enzymes of sphingolipid metabolism in Drosophila melanogaster","volume":"62","author":"Acharya","year":"2005","journal-title":"Cell. 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