ArticleNature communications2025
Transport and inhibition of the sphingosine-1-phosphate exporter SPNS2.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Endothelial Collapse as a Convergent Immunovascular Phenotype in Sepsis and Severe Arboviral Disease: The SIMVAC Model.Pathogens (Basel, Switzerland) · 2026Review
- 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
- 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
- Covalently constrained 'Di-Gembodies' enable parallel structure solutions by cryo-EM.Nature chemical biology · 2026Article
- Erythrocytes as a Source of Exerkines.International journal of molecular sciences · 2025Review
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Assessment of Spinster homologue 2 (Spns2)-dependent transport of sphingosine-1-phosphate as a therapeutic target.British journal of pharmacology · 2025Article
Corrections and comments
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Authors and funding
27 authors.
Funding
Abstract
Sphingosine-1-phosphate (S1P) is a signaling lysolipid critical to heart development, immunity, and hearing. Accordingly, mutations in the S1P transporter SPNS2 are associated with reduced white cell count and hearing defects. SPNS2 also exports the S1P-mimicking FTY720-P (Fingolimod) and thereby is central to the pharmacokinetics of this drug when treating multiple sclerosis. Here, we use a combination of cryo-electron microscopy, immunofluorescence, in vitro binding and in vivo S1P export assays, and molecular dynamics simulations to probe SPNS2's substrate binding and transport. These results reveal the transporter's binding mode to its native substrate S1P, the therapeutic FTY720-P, and the reported SPNS2-targeting inhibitor 33p. Further capturing an inward-facing apo state, our structures illuminate the protein's mechanism for exchange between inward-facing and outward-facing conformations. Finally, using these structural, localization, and S1P transport results, we identify how pathogenic mutations ablate the protein's export activity and thereby lead to hearing loss.
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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.