MFSD1

Last update 23 Jan 2025

Basic Info

Synonyms

FLJ14153, major facilitator superfamily domain containing 1, Major facilitator superfamily domain-containing protein 1

+ [6]

Introduction

Lysosomal transporter which is essential for liver homeostasis. Required to maintain stability and lysosomal localization of GLMP.

100 Clinical Results associated with MFSD1

100 Translational Medicine associated with MFSD1

0 Patents (Medical) associated with MFSD1

Literatures (Medical) associated with MFSD1

12 Oct 2024·Future Microbiology

Expression of Plasmodium major facilitator superfamily protein in transporters – Δ Candida identifies a drug transporter

Article

Author: Singh, Harshita ; Gupta, Aashima ; Jain, Ravi ; Maurya, Preeti ; Kumar, Mohit ; Thaer Abdulhameed Almuqdadi, Haider ; Singh, Shailja ; Gaur, Naseem A ; Arenz, Christoph

Aim: To assess the functional relevance of a putative Major Facilitator Superfamily protein (PF3D7_0210300; 'PfMFSDT') as a drug transporter, using Candida glabrata for orthologous protein expression.Methods: Complementary Determining Sequence encoding PfMFSDT was integrated into the genome of genetically engineered C. glabrata strain MSY8 via homologous recombination, followed by assessing its functional relevance as a drug transporter.Results & conclusion: The modified C. glabrata strain exhibited plasma membrane localization of PfMFSDT and characteristics of an Major Facilitator Superfamily transporter, conferring resistance to antifungals, ketoconazole and itraconazole. The nanomolar inhibitory effects of the drugs on the intra-erythrocytic growth of Plasmodium falciparum highlight their antimalarial properties. This study proposes PfMFSDT as a drug transporter, expanding the repertoire of the currently known antimalarial 'resistome'.

01 Jul 2024·Nature Cell Biology

MFSD1 with its accessory subunit GLMP functions as a general dipeptide uniporter in lysosomes

Article

Author: Dong, Wentao ; McCort-Tranchepain, Isabelle ; Sato, Kenji ; Löw, Christian ; Laqtom, Nouf N ; Guelle, Océane ; Gabriel, Florian ; Mehdipour, Ahmad Reza ; Debacker, Cécile ; Abu-Remaileh, Monther ; Gasnier, Bruno ; Ejima, Akika ; Kotov, Vadim ; Iguchi, Miharu ; Saftig, Paul ; Jungnickel, Katharina Esther Julia ; Dairou, Julien ; Damme, Markus ; Chan, Sze Ham ; Massa López, David

AbstractThe lysosomal degradation of macromolecules produces diverse small metabolites exported by specific transporters for reuse in biosynthetic pathways. Here we deorphanized the major facilitator superfamily domain containing 1 (MFSD1) protein, which forms a tight complex with the glycosylated lysosomal membrane protein (GLMP) in the lysosomal membrane. Untargeted metabolomics analysis of MFSD1-deficient mouse lysosomes revealed an increase in cationic dipeptides. Purified MFSD1 selectively bound diverse dipeptides, while electrophysiological, isotope tracer and fluorescence-based studies in Xenopus oocytes and proteoliposomes showed that MFSD1–GLMP acts as a uniporter for cationic, neutral and anionic dipeptides. Cryoelectron microscopy structure of the dipeptide-bound MFSD1–GLMP complex in outward-open conformation characterized the heterodimer interface and, in combination with molecular dynamics simulations, provided a structural basis for its selectivity towards diverse dipeptides. Together, our data identify MFSD1 as a general lysosomal dipeptide uniporter, providing an alternative route to recycle lysosomal proteolysis products when lysosomal amino acid exporters are overloaded.

26 Mar 2024·Proceedings of the National Academy of SciencesQ1 · CROSS-FIELD

Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport

Q1 · CROSS-FIELD

Article

Author: Siekhaus, Daria ; Madej, Gregor M ; Sitte, Harald H ; Sandtner, Walter ; Blaha, Nadine ; Horn, Georg ; Boytsov, Danila ; Ziegler, Christine ; Köcher, Thomas ; Roblek, Marko

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.

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MFSD1

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