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Serine restriction alters sphingolipid diversity to constrain tumour growth
In xenograft tumour models in mice, modulation of dietary serine, serine palmitoyltransferase or phosphoglycerate dehydrogenase activity enables control of the endogenous synthesis of deoxysphingolipids, sensitizing the tumours to metabolic stress and slowing their progression.
- Thangaselvam Muthusamy
- , Thekla Cordes
- & Christian M. Metallo
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Letter |
Mfsd2b is essential for the sphingosine-1-phosphate export in erythrocytes and platelets
Identification of a transmembrane protein, Mfsd2b, that is essential for the export of the signalling molecule sphingosine-1-phosphate (S1P) from red blood cells and platelets.
- Thiet M. Vu
- , Ayako-Nakamura Ishizu
- & Long N. Nguyen
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Letter |
HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation
Apolipoprotein-M-bound sphingosine-1-phosphate (S1P) is found to restrain the generation of new lymphocytes—and, consequently, adaptive immune responses—by activating the S1P1 receptor on bone marrow lymphocyte progenitors in mice.
- Victoria A. Blaho
- , Sylvain Galvani
- & Timothy Hla
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Letter |
Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids
A human lipid transfer protein (GLTPD1, named here CPTP) is shown to regulate eicosanoid production by mediating the intermembrane transfer of the phosphorylated sphingolipid ceramide-1-phosphate through a non-vesicular transport mechanism elucidated by structural, functional and biological data.
- Dhirendra K. Simanshu
- , Ravi Kanth Kamlekar
- & Dinshaw J. Patel
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Letter |
Molecular recognition of a single sphingolipid species by a protein’s transmembrane domain
A sphingomyelin-binding motif is identified in the membrane-spanning domain of p24, a COPI machinery protein.
- F.-Xabier Contreras
- , Andreas M. Ernst
- & Britta Brügger
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Letter |
Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2
Engagement of the tumour-necrosis factor (TNF) receptor results in the assembly of multi-component signalling complexes by adaptor proteins that include TNF receptor-associated factor 2 (TRAF2). Genetic evidence indicates that TRAF2 is needed for the polyubiquitination of receptor interacting protein 1 (RIP1), but direct evidence has been lacking. Here it is shown that the lipid sphingosine-1-phosphate is a co-factor needed for this ubiquitination activity of TRAF2.
- Sergio E. Alvarez
- , Kuzhuvelil B. Harikumar
- & Sarah Spiegel
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Article |
Orm family proteins mediate sphingolipid homeostasis
Mutations near the ORMDL3 gene have been associated with childhood asthma. Here, in yeast, Orm proteins are shown to function in sphingolipid homeostasis; alterations in this control result in misregulation of sphingolipid production and accumulation of toxic metabolites. This raises the testable hypothesis that misregulation of sphingolipids may directly contribute to the development of asthma.
- David K. Breslow
- , Sean R. Collins
- & Jonathan S. Weissman