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Int. J. Mol. Sci. 2016, 17(10), 1761;

Role of Intracellular Lipid Logistics in the Preferential Usage of Very Long Chain-Ceramides in Glucosylceramide

Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University, Chiyoda-ku, Tokyo 101-8308, Japan
Author to whom correspondence should be addressed.
Academic Editor: Cheorl-Ho Kim
Received: 12 July 2016 / Revised: 11 October 2016 / Accepted: 14 October 2016 / Published: 21 October 2016
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Ceramide is a common precursor of sphingomyelin (SM) and glycosphingolipids (GSLs) in mammalian cells. Ceramide synthase 2 (CERS2), one of the six ceramide synthase isoforms, is responsible for the synthesis of very long chain fatty acid (C20–26 fatty acids) (VLC)-containing ceramides (VLC-Cer). It is known that the proportion of VLC species in GSLs is higher than that in SM. To address the mechanism of the VLC-preference of GSLs, we used genome editing to establish three HeLa cell mutants that expressed different amounts of CERS2 and compared the acyl chain lengths of SM and GSLs by metabolic labeling experiments. VLC-sphingolipid expression was increased along with that of CERS2, and the proportion of VLC species in glucosylceramide (GlcCer) was higher than that in SM for all expression levels of CERS2. This higher proportion was still maintained even when the proportion of C16-Cer to the total ceramides was increased by disrupting the ceramide transport protein (CERT)-dependent C16-Cer delivery pathway for SM synthesis. On the other hand, merging the Golgi apparatus and the endoplasmic reticulum (ER) by Brefeldin A decreased the proportion of VLC species in GlcCer probably due to higher accessibility of UDP-glucose ceramide glucosyltransferase (UGCG) to C16-rich ceramides. These results suggest the existence of a yet-to-be-identified mechanism rendering VLC-Cer more accessible than C16-Cer to UGCG, which is independent of CERT. View Full-Text
Keywords: genome editing; sphingolipid; ceramide synthase; glucosylceramide; sphingomyelin; CERT genome editing; sphingolipid; ceramide synthase; glucosylceramide; sphingomyelin; CERT

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Yamaji, T.; Horie, A.; Tachida, Y.; Sakuma, C.; Suzuki, Y.; Kushi, Y.; Hanada, K. Role of Intracellular Lipid Logistics in the Preferential Usage of Very Long Chain-Ceramides in Glucosylceramide. Int. J. Mol. Sci. 2016, 17, 1761.

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