Evidence map›Paper›PMID 38839979›Full record

ArticleNature cell biology2024

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

Katharina Esther Julia Jungnickel, Océane Guelle, Miharu Iguchi, Wentao Dong, Vadim Kotov, Florian Gabriel, Cécile Debacker, Julien Dairou, Isabelle McCort-Tranchepain, Nouf N Laqtom and 10 more

Abstract read
In one paragraph

Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Katharina Esther Julia Jungnickel *Centre for Structural Systems Biology, Hamburg, Germany.ORCID 0000-0002-2850-5911
Océane Guelle *Saints-Pères Paris Institute for the Neurosciences, Université Paris Cité, Centre National de la Recherche Scientifique, Paris, France.ORCID 0000-0002-4362-9824
Miharu IguchiDepartment of Chemical Engineering, Stanford University, Stanford, CA, USA.
Wentao DongDepartment of Chemical Engineering, Stanford University, Stanford, CA, USA.ORCID 0000-0001-5490-4265
Vadim KotovCentre for Structural Systems Biology, Hamburg, Germany.
Florian GabrielCentre for Structural Systems Biology, Hamburg, Germany.
Cécile DebackerSaints-Pères Paris Institute for the Neurosciences, Université Paris Cité, Centre National de la Recherche Scientifique, Paris, France.
Julien DairouLaboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS UMR 8601, Université Paris Cité, Paris, France.
Isabelle McCort-TranchepainLaboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS UMR 8601, Université Paris Cité, Paris, France.
Nouf N LaqtomDepartment of Chemical Engineering, Stanford University, Stanford, CA, USA.
Sze Ham ChanDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA.
Akika EjimaGraduate School of Agriculture, Kyoto University, Kyoto, Japan.
Kenji SatoGraduate School of Agriculture, Kyoto University, Kyoto, Japan.
David Massa LópezInstitute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany.
Paul SaftigInstitute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany.ORCID 0000-0003-2637-7052
Ahmad Reza MehdipourUGent Center for Molecular Modeling, Ghent University, Ghent, Belgium.
Monther Abu-RemailehDepartment of Chemical Engineering, Stanford University, Stanford, CA, USA.
Bruno GasnierSaints-Pères Paris Institute for the Neurosciences, Université Paris Cité, Centre National de la Recherche Scientifique, Paris, France. bruno.gasnier@u-paris.fr.ORCID 0000-0003-4458-6296
Christian LöwCentre for Structural Systems Biology, Hamburg, Germany. christian.loew@embl-hamburg.de.ORCID 0000-0003-0764-7483
Markus DammeInstitute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany. mdamme@biochem.uni-kiel.de.ORCID 0000-0002-9699-9351

Funding

Agence Nationale de la Recherche (French National Research Agency) ANR-22-CE11-0008Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 05K18YEADeutsche Forschungsgemeinschaft (German Research Foundation) 1785-1
6 · The paper itself

Abstract

The 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.

Indexed as

DipeptidesLysosomesAnimalsCryoelectron MicroscopyFemaleHumansMiceMice, KnockoutMolecular Dynamics SimulationOocytesSymportersTransient Receptor Potential ChannelsXenopus laevisDipeptidesMcoln1 protein, mouseSymportersTransient Receptor Potential Channels

Identifiers

PMID38839979
PMCPMC11252000

What OpenQuestion holds

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Registered trials

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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.