Back to Search
Start Over
A multi-hierarchical approach reveals d-serine as a hidden substrate of sodium-coupled monocarboxylate transporters
- Source :
- eLife, Vol 12 (2024)
- Publication Year :
- 2024
- Publisher :
- eLife Sciences Publications Ltd, 2024.
-
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.
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 12
- Database :
- Directory of Open Access Journals
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.712df96a4ef54e3b881a8aba60b55281
- Document Type :
- article
- Full Text :
- https://doi.org/10.7554/eLife.92615