EPT1 (selenoprotein I) is critical for the neural development and maintenance of plasmalogen in humans[S]
Ethanolamine phosphotransferase (EPT)1, also known as selenoprotein 1 (SELENOI), is an enzyme that transfers phosphoethanolamine from cytidine diphosphate-ethanolamine to lipid acceptors to produce ethanolamine glycerophospholipids, such as diacyl-linked phosphatidylethanolamine (PE) and ether-linke...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752033100X |
| _version_ | 1818958134495936512 |
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| author | Yasuhiro Horibata Orly Elpeleg Ayelet Eran Yoshio Hirabayashi David Savitzki Galit Tal Hanna Mandel Hiroyuki Sugimoto |
| author_facet | Yasuhiro Horibata Orly Elpeleg Ayelet Eran Yoshio Hirabayashi David Savitzki Galit Tal Hanna Mandel Hiroyuki Sugimoto |
| author_sort | Yasuhiro Horibata |
| collection | DOAJ |
| description | Ethanolamine phosphotransferase (EPT)1, also known as selenoprotein 1 (SELENOI), is an enzyme that transfers phosphoethanolamine from cytidine diphosphate-ethanolamine to lipid acceptors to produce ethanolamine glycerophospholipids, such as diacyl-linked phosphatidylethanolamine (PE) and ether-linked plasmalogen [1-alkenyl-2-acyl-glycerophosphoethanolamine (plasmenyl-PE)]. However, to date there has been no analysis of the metabolomic consequences of the mutation of EPT1 on the concentration of ethanolamine glycerophospholipids in mammalian cells. We studied a patient with severe complicated hereditary spastic paraplegia, sensorineural-deafness, blindness, and seizures. Neuroimaging revealed hypomyelination, followed by brain atrophy mainly in the cerebellum and brainstem. Using whole exome sequencing, we identified a novel EPT1 mutation (exon skipping). In vitro EPT activity, as well as the rate of biosynthesis of ethanolamine glycerophospholipids, was markedly reduced in cultures of the patient's skin fibroblasts. Quantification of phospholipids by LC-MS/MS demonstrated reduced levels of several PE species with polyunsaturated fatty acids, such as 38:6, 38:4, 40:6, 40:5, and 40:4. Notably, most plasmenyl-PE species were significantly decreased in the patient's cells, whereas most plasmanylcholine [1-alkyl-2-acyl-glycerophosphocholine (plasmanyl-PC)] species were increased. Similar findings regarding decreased plasmenyl-PE and increased plasmanyl-PC were obtained using EPT1-KO HeLa cells. Our data demonstrate for the first time the indispensable role of EPT1 in the myelination process and neurodevelopment, and in the maintenance of normal homeostasis of ether-linked phospholipids in humans. |
| first_indexed | 2024-12-20T11:20:55Z |
| format | Article |
| id | doaj.art-243f9fa72f1442b886b7c3fba462b628 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T11:20:55Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-243f9fa72f1442b886b7c3fba462b6282022-12-21T19:42:31ZengElsevierJournal of Lipid Research0022-22752018-01-0159610151026EPT1 (selenoprotein I) is critical for the neural development and maintenance of plasmalogen in humans[S]Yasuhiro Horibata0Orly Elpeleg1Ayelet Eran2Yoshio Hirabayashi3David Savitzki4Galit Tal5Hanna Mandel6Hiroyuki Sugimoto7Department of Biochemistry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, JapanMonique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, IsraelDepartment of Diagnostic Imaging, Rambam Health Care Campus, Haifa, IsraelMolecular Membrane Neuroscience, RIKEN Brain Science Institute, Wako, Saitama, JapanPediatric Neurology Unit, Galilee Medical Center, Nahariya, IsraelMetabolic Unit, Rambam Health Care Campus, Rappaport School of Medicine, Haifa, IsraelTo whom correspondence should be addressed.; Metabolic Unit, Rambam Health Care Campus, Rappaport School of Medicine, Haifa, IsraelTo whom correspondence should be addressed.; Department of Biochemistry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, JapanEthanolamine phosphotransferase (EPT)1, also known as selenoprotein 1 (SELENOI), is an enzyme that transfers phosphoethanolamine from cytidine diphosphate-ethanolamine to lipid acceptors to produce ethanolamine glycerophospholipids, such as diacyl-linked phosphatidylethanolamine (PE) and ether-linked plasmalogen [1-alkenyl-2-acyl-glycerophosphoethanolamine (plasmenyl-PE)]. However, to date there has been no analysis of the metabolomic consequences of the mutation of EPT1 on the concentration of ethanolamine glycerophospholipids in mammalian cells. We studied a patient with severe complicated hereditary spastic paraplegia, sensorineural-deafness, blindness, and seizures. Neuroimaging revealed hypomyelination, followed by brain atrophy mainly in the cerebellum and brainstem. Using whole exome sequencing, we identified a novel EPT1 mutation (exon skipping). In vitro EPT activity, as well as the rate of biosynthesis of ethanolamine glycerophospholipids, was markedly reduced in cultures of the patient's skin fibroblasts. Quantification of phospholipids by LC-MS/MS demonstrated reduced levels of several PE species with polyunsaturated fatty acids, such as 38:6, 38:4, 40:6, 40:5, and 40:4. Notably, most plasmenyl-PE species were significantly decreased in the patient's cells, whereas most plasmanylcholine [1-alkyl-2-acyl-glycerophosphocholine (plasmanyl-PC)] species were increased. Similar findings regarding decreased plasmenyl-PE and increased plasmanyl-PC were obtained using EPT1-KO HeLa cells. Our data demonstrate for the first time the indispensable role of EPT1 in the myelination process and neurodevelopment, and in the maintenance of normal homeostasis of ether-linked phospholipids in humans.http://www.sciencedirect.com/science/article/pii/S002222752033100Xphospholipids/phosphatidylethanolaminephospholipids/phosphatidylcholinephospholipids/biosynthesisphospholipids/metabolismethanolamine phosphotransferase 1neurodegenerative disease |
| spellingShingle | Yasuhiro Horibata Orly Elpeleg Ayelet Eran Yoshio Hirabayashi David Savitzki Galit Tal Hanna Mandel Hiroyuki Sugimoto EPT1 (selenoprotein I) is critical for the neural development and maintenance of plasmalogen in humans[S] Journal of Lipid Research phospholipids/phosphatidylethanolamine phospholipids/phosphatidylcholine phospholipids/biosynthesis phospholipids/metabolism ethanolamine phosphotransferase 1 neurodegenerative disease |
| title | EPT1 (selenoprotein I) is critical for the neural development and maintenance of plasmalogen in humans[S] |
| title_full | EPT1 (selenoprotein I) is critical for the neural development and maintenance of plasmalogen in humans[S] |
| title_fullStr | EPT1 (selenoprotein I) is critical for the neural development and maintenance of plasmalogen in humans[S] |
| title_full_unstemmed | EPT1 (selenoprotein I) is critical for the neural development and maintenance of plasmalogen in humans[S] |
| title_short | EPT1 (selenoprotein I) is critical for the neural development and maintenance of plasmalogen in humans[S] |
| title_sort | ept1 selenoprotein i is critical for the neural development and maintenance of plasmalogen in humans s |
| topic | phospholipids/phosphatidylethanolamine phospholipids/phosphatidylcholine phospholipids/biosynthesis phospholipids/metabolism ethanolamine phosphotransferase 1 neurodegenerative disease |
| url | http://www.sciencedirect.com/science/article/pii/S002222752033100X |
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