ArticleeLife2024
<sc>A</sc> multi-hierarchical approach reveals <sc>d</sc>-serine as a hidden substrate of sodium-coupled monocarboxylate transporters.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- Human endogenous retrovirus envelope proteins alter extracellular vesicle cellular interactions and biodistribution.bioRxiv : the preprint server for biology · 2026Article
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- d-Alanine, a Circadian Metabolite that Regulates Glucose Metabolism and Viral Infection.Chembiochem : a European journal of chemical biology · 2025Review
- Plasma D-asparagine and the D/L-serine ratio reflect chronic kidney diseases in children regardless of physique.Amino acids · 2024Article
- D-Serine as a sensor and effector of the kidney.Clinical and experimental nephrology · 2023Review
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
Transporter research primarily relies on the canonical substrates of well-established transporters. This approach has limitations when studying transporters for the low-abundant micromolecules, such as micronutrients, and may not reveal physiological functions of the transporters. While d-serine, a trace enantiomer of serine in the circulation, was discovered as an emerging biomarker of kidney function, its transport mechanisms in the periphery remain unknown. Here, using a multi-hierarchical approach from body fluids to molecules, combining multi-omics, cell-free synthetic biochemistry, and ex vivo transport analyses, we have identified two types of renal d-serine transport systems. We revealed that the small amino acid transporter ASCT2 serves as a d-serine transporter previously uncharacterized in the kidney and discovered d-serine as a non-canonical substrate of the sodium-coupled monocarboxylate transporters (SMCTs). These two systems are physiologically complementary, but ASCT2 dominates the role in the pathological condition. Our findings not only shed light on renal d-serine transport, but also clarify the importance of non-canonical substrate transport. This study provides a framework for investigating multiple transport systems of various trace micromolecules under physiological conditions and in multifactorial diseases.
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Registered trials
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