ArticleNature2017
Mfsd2b is essential for the sphingosine-1-phosphate export in erythrocytes and platelets.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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Who cites it
149 citing papers in PubMed, 233 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Structure and mechanism of human sphingosine-1-phosphate transporter MFSD2B.Nature communications · 2026Article
- Sphingolipids and Atherosclerosis.Current atherosclerosis reports · 2026Review
- Acute pain transfusion reaction in a patient with thalassemia: In-depth characterization of short- and long-term phenotypes.Transfusion · 2026Article
- Sphingolipid Signaling in Vascular Smooth Muscle Cells during Development and Diseases.JMA journal · 2026Review
- Integrated Serum Pharmacochemistry, Metabolomics, and Network Pharmacology to Reveal the Material Basis and Mechanism of Juan-tong-yin in the Treatment of Endometriosis.Applied biochemistry and biotechnology · 2026Article
- Insufficient erythrocyte-derived S1P: A pathogenic driver and diagnostic biolipid for tumor progression.iScience · 2026Article
- Review
- Structural insights into subtype-specific agonist recognition by sphingosine-1-phosphate receptors.PLoS biology · 2026Article
- Apolipoprotein M: Structural insights, functional roles, and therapeutic approaches in vascular disease.The Journal of biological chemistry · 2026Review
- Invasion preferences suggest a possible role for Plasmodium falciparum parasites in the expansion of Duffy negativity in West and Central Africa.Molecular biology and evolution · 2026Article
- Structure and mechanism of human sphingosine-1-phosphate transporter MFSD2B.bioRxiv : the preprint server for biology · 2026Article
- Sphingosine-1-Phosphate Regulation to Alleviate Sickle Cell Disease Severity: A Promising Therapeutic Approach.Saudi medical journal · 2026Review
- MFSD2A in Focus: the Molecular Mechanism of Omega-3 Fatty Acid Transport.Physiology (Bethesda, Md.) · 2025Review
- Article
- Assessment of Spinster homologue 2 (Spns2)-dependent transport of sphingosine-1-phosphate as a therapeutic target.British journal of pharmacology · 2025Article
- Time Course of Plasma Proteomic and Oxylipin Changes Induced by LPS Challenge and Modulated by Antioxidant Supplementation in a Randomized Controlled Trial.Antioxidants (Basel, Switzerland) · 2025Article
- Small Molecules in the Treatment of Acute Severe Ulcerative Colitis: A Review of Current Evidence.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Molecular basis of Spns1-mediated lysophospholipid transport from the lysosome.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Apolipoprotein M expression modifies the sphingolipid landscape in murine blood and lymph.Frontiers in immunology · 2025Article
89 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingosine-1-phosphate (S1P), a potent signalling lipid secreted by red blood cells and platelets, plays numerous biologically significant roles. However, the identity of its long-sought exporter is enigmatic. Here we show that the major facilitator superfamily transporter 2b (Mfsd2b), an orphan transporter, is essential for S1P export from red blood cells and platelets. Comprehensive lipidomic analysis indicates a dramatic and specific accumulation of S1P species in Mfsd2b knockout red blood cells and platelets compared with that of wild-type controls. Consistently, biochemical assays from knockout red blood cells, platelets, and cell lines overexpressing human and mouse Mfsd2b proteins demonstrate that Mfsd2b actively exports S1P. Plasma S1P level in knockout mice is significantly reduced by 42-54% of that of wild-type level, indicating that Mfsd2b pathway contributes approximately half of the plasma S1P pool. The reduction of plasma S1P in knockout mice is insufficient to cause blood vessel leakiness, but it does render the mice more sensitive to anaphylactic shock. Stress-induced erythropoiesis significantly increased plasma S1P levels and knockout mice were sensitive to these treatments. Surprisingly, knockout mice exhibited haemolysis associated with red blood cell stomatocytes, and the haemolytic phenotype was severely increased with signs of membrane fragility under stress erythropoiesis. We show that S1P secretion by Mfsd2b is critical for red blood cell morphology. Our data reveal an unexpected physiological role of red blood cells in sphingolipid metabolism in circulation. These findings open new avenues for investigating the signalling roles of S1P derived from red blood cells and platelets.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.