Boytsov, Danila and Madej, Gregor M. and Horn, Georg and Blaha, Nadine and Koecher, Thomas and Sitte, Harald H. and Siekhaus, Daria and Ziegler, Christine M. and Sandtner, Walter and Roblek, Marko (2024) Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 121 (13): e231968612. ISSN 0027-8424, 1091-6490
Full text not available from this repository. (Request a copy)Abstract
Orphan solute carrier (SLC) represents a group of membrane transporters whose exact functions and substrate specificities are not known. Elucidating the function and regulation of orphan SLC transporters is not only crucial for advancing our knowledge of cellular and molecular biology but can potentially lead to the development of new therapeutic strategies. Here, we provide evidence for the biological function of a ubiquitous orphan lysosomal SLC, the Major Facilitator Superfamily Domain- containing Protein 1 (MFSD1), which has remained phylogenetically unassigned. Targeted metabolomics revealed that dipeptides containing either lysine or arginine residues accumulate in lysosomes of cells lacking MFSD1. Whole - cell patch - clamp electrophysiological recordings of HEK293-cells expressing MFSD1 on the cell surface displayed transport affinities for positively charged dipeptides in the lower mM range, while dipeptides that carry a negative net charge were not transported. This was also true for single amino acids and tripeptides, which MFSD1 failed to transport. Our results identify MFSD1 as a highly selective lysosomal lysine/arginine/histidine- containing dipeptide exporter, which functions as a uniporter.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | deorphanization of SLC MFSD1; targeted metabolomics; electrophysiology; dipeptides; lysosomes |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Christine Ziegler |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Dec 2025 06:34 |
| Last Modified: | 16 Dec 2025 06:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65126 |
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