{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:52:07Z","timestamp":1790499127855,"version":"4.1.0"},"reference-count":53,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,2,16]]},"abstract":"<jats:p>Lipid movement between organelles is a critical component of eukaryotic membrane homeostasis. Niemann Pick type C (NP-C) disease is a fatal neurodegenerative disorder typified by lysosomal accumulation of cholesterol and sphingolipids. Expression of yeast NP-C\u2013related gene 1 (NCR1), the orthologue of the human NP-C gene 1 (NPC1) defective in the disease, in Chinese hamster ovary NPC1 mutant cells suppressed lipid accumulation. Deletion of NCR1, encoding a transmembrane glycoprotein predominantly residing in the vacuole of normal yeast, gave no phenotype. However, a dominant mutation in the putative sterol-sensing domain of Ncr1p conferred temperature and polyene antibiotic sensitivity without changes in sterol metabolism. Instead, the mutant cells were resistant to inhibitors of sphingolipid biosynthesis and super sensitive to sphingosine and C2-ceramide. Moreover, plasma membrane sphingolipids accumulated and redistributed to the vacuole and other subcellular membranes of the mutant cells. We propose that the primordial function of these proteins is to recycle sphingolipids and that defects in this process in higher eukaryotes secondarily result in cholesterol accumulation.<\/jats:p>","DOI":"10.1083\/jcb.200310046","type":"journal-article","created":{"date-parts":[[2004,2,17]],"date-time":"2004-02-17T20:36:29Z","timestamp":1077050189000},"page":"547-556","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":123,"title":["Mutagenesis of the putative sterol-sensing domain of yeast Niemann Pick C\u2013related protein reveals a primordial role in subcellular sphingolipid distribution"],"prefix":"10.1083","volume":"164","author":[{"given":"Krishnamurthy","family":"Malathi","sequence":"first","affiliation":[{"name":"1Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumi","family":"Higaki","sequence":"additional","affiliation":[{"name":"1Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur H.","family":"Tinkelenberg","sequence":"additional","affiliation":[{"name":"1Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina A.","family":"Balderes","sequence":"additional","affiliation":[{"name":"1Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorca","family":"Almanzar-Paramio","sequence":"additional","affiliation":[{"name":"2Department of Pharmacology, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa J.","family":"Wilcox","sequence":"additional","affiliation":[{"name":"1Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naz","family":"Erdeniz","sequence":"additional","affiliation":[{"name":"3Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Redican","sequence":"additional","affiliation":[{"name":"1Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahajabeen","family":"Padamsee","sequence":"additional","affiliation":[{"name":"1Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"1Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohail","family":"Khan","sequence":"additional","affiliation":[{"name":"1Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Alcantara","sequence":"additional","affiliation":[{"name":"1Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene D.","family":"Carstea","sequence":"additional","affiliation":[{"name":"5National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"Morris","sequence":"additional","affiliation":[{"name":"5National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Sturley","sequence":"additional","affiliation":[{"name":"1Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032"},{"name":"4Department of Pediatrics, Columbia University Medical Center, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2004,2,17]]},"reference":[{"key":"2023072905130447400_BIB1","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","volume":"25","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"2023072905130447400_BIB2"},{"key":"2023072905130447400_BIB3","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1073\/pnas.97.7.3254","volume":"97","year":"2000","journal-title":"Proc. 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