The Ormdl genes regulate the sphingolipid synthesis pathway to ensure proper myelination and neurologic function in mice
作者: Benjamin A ClarkeSaurav MajumderHongling ZhuY Terry LeeMari KonoCuiling LiCaroline KhannaHailey BlainRonit SchwartzVienna L HusoColleen ByrnesGalina TuymetovaTeresa M DunnMaria L AllendeRichard L Proia
作者单位: 11 Genetics of Development and Disease Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Bethesda United States
22 Department of Biochemistry Uniformed Services University of the Health Sciences Bethesda United States
刊名: eLife, 2019, Vol.8
来源数据库: eLife Sciences Publications, Ltd
DOI: 10.7554/eLife.51067
关键词: SphingolipidsMyelinationMouse modelsMetabolism
原始语种摘要: Sphingolipids are membrane and bioactive lipids that are required for many aspects of normal mammalian development and physiology. However, the importance of the regulatory mechanisms that control sphingolipid levels in these processes is not well understood. The mammalian ORMDL proteins (ORMDL1, 2 and 3) mediate feedback inhibition of the de novo synthesis pathway of sphingolipids by inhibiting serine palmitoyl transferase in response to elevated ceramide levels. To understand the function of ORMDL proteins in vivo, we studied mouse knockouts (KOs) of the Ormdl genes. We found that Ormdl1 and Ormdl3 function redundantly to suppress the levels of bioactive sphingolipid metabolites during myelination of the sciatic nerve. Without proper ORMDL-mediated regulation of sphingolipid synthesis,...
全文获取路径: eLife科学出版社  (合作)
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关键词翻译
关键词翻译
  • sphingolipid 鞘脂类
  • myelination 髓鞘生成
  • pathway 轨道
  • regulate 控制
  • synthesis 合成
  • bioactive 对活质起作用的
  • understood 明白
  • proper 合适的
  • regulatory 控制的
  • mammalian 哺乳动物