ArticleCell2023
Structural and functional insights into Spns2-mediated transport of sphingosine-1-phosphate.
Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Single-Cell Meta-Analysis Uncovers the Pancreatic Endothelial Cell Transcriptomic Signature and Reveals a Key Role for NKX2-3 in PLVAP Expression.Arteriosclerosis, thrombosis, and vascular biology · 2024Pooled it
- Structure and mechanism of human sphingosine-1-phosphate transporter MFSD2B.Nature communications · 2026Article
- Proton-coupled alternating access in a versatile mycobacterial Spns drug transporter.Research square · 2026Article
- Proton-coupled alternating access in a versatile mycobacterial Spns drug transporter.bioRxiv : the preprint server for biology · 2026Article
- From Lysosomal Storage to Neurodegeneration: Sphingolipid Signaling as a Driver of CNS Pathology and Biomarker Strategy in Neuronopathic Gaucher Disease.International journal of molecular sciences · 2026Review
- Microglia-independent rAAV-induced inflammation causes persistent ocular immune dysregulation rescued by S1P receptor modulation.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- SPNS2 exports sphingosine-1-phosphate and imports glucose.Nature communications · 2026Article
- Structure and mechanism of human sphingosine-1-phosphate transporter MFSD2B.bioRxiv : the preprint server for biology · 2026Article
- A Spinster-like Transporter at the Inner Membrane Complex is critical for Toxoplasma gondii cytokinesis, motility and invasion.PLoS pathogens · 2026Article
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- Sphingosine-1-Phosphate Regulation to Alleviate Sickle Cell Disease Severity: A Promising Therapeutic Approach.Saudi medical journal · 2026Review
- Covalently constrained 'Di-Gembodies' enable parallel structure solutions by cryo-EM.Nature chemical biology · 2026Article
- Genome-wide Association Studies of the Pathogenic Sphingosine-1-Phosphate Gene in Ulcerative ColitisEndocrine, metabolic & immune disorders drug targets · 2026Article
- CEBPD-mediated SGPP2 upregulation via PERK/ER stress in endothelial cells disrupts S1P homeostasis and impairs angiogenesis in chronic endometritis.Journal of translational medicine · 2025Article
- SPNS1 is an essential cellular factor for EV-A71 by acting as a transporter of viral pocket factor.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular basis of prostaglandin ENature communications · 2025Article
- Structural pharmacology of SV2A reveals an allosteric modulation mechanism in the major facilitator superfamily.Nature communications · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Structure of human mitochondrial pyruvate carrier MPC1 and MPC2 complex.Nature communications · 2025Article
- Lysosomal quality control Review.Autophagy · 2025Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Sphingosine-1-phosphate (S1P) is an important signaling sphingolipid that regulates the immune system, angiogenesis, auditory function, and epithelial and endothelial barrier integrity. Spinster homolog 2 (Spns2) is an S1P transporter that exports S1P to initiate lipid signaling cascades. Modulating Spns2 activity can be beneficial in treatments of cancer, inflammation, and immune diseases. However, the transport mechanism of Spns2 and its inhibition remain unclear. Here, we present six cryo-EM structures of human Spns2 in lipid nanodiscs, including two functionally relevant intermediate conformations that link the inward- and outward-facing states, to reveal the structural basis of the S1P transport cycle. Functional analyses suggest that Spns2 exports S1P via facilitated diffusion, a mechanism distinct from other MFS lipid transporters. Finally, we show that the Spns2 inhibitor 16d attenuates the transport activity by locking Spns2 in the inward-facing state. Our work sheds light on Spns2-mediated S1P transport and aids the development of advanced Spns2 inhibitors.
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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.