Evidence map›Paper›PMID 28637874›Full record

ArticleThe Journal of biological chemistry2017

Direct demonstration of a neonatal Fc receptor (FcRn)-driven endosomal sorting pathway for cellular recycling of albumin.

Esben G W Schmidt, Michael L Hvam, Filipa Antunes, Jason Cameron, Dorthe Viuff, Birgitte Andersen, Nanna N Kristensen, Kenneth A Howard

Open access · hybridAbstract readComparative Study
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
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

47 citing papers in PubMed, 78 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Article
  5. Ozoralizumab, a trivalent anti-TNFα NANOBODYFrontiers in immunology · 2026
    Article
  6. Endothelial cells sialylate IgG within the FcRn-mediated recycling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Review
  8. Unveiling role of serum albumin in disaggregation and cellular delivery of a near-infrared chlorophyll-based photosensitizer in breast cancer cells.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. FcRn-guided antigen trafficking enhances cancer vaccine efficacy.Cancer immunology, immunotherapy : CII · 2025
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Article
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

8 authors at 3 institutions in 2 countries.

Esben G W SchmidtFrom the Novozymes A/S, 2880 Bagsværd, Denmark.
Michael L HvamInterdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark, and.
Filipa AntunesAlbumedix Ltd., NG7 1FD Nottingham, United Kingdom.
Jason CameronAlbumedix Ltd., NG7 1FD Nottingham, United Kingdom.
Dorthe ViuffFrom the Novozymes A/S, 2880 Bagsværd, Denmark.
Birgitte AndersenFrom the Novozymes A/S, 2880 Bagsværd, Denmark.
Nanna N KristensenFrom the Novozymes A/S, 2880 Bagsværd, Denmark.
Kenneth A HowardInterdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark, and kenh@inano.au.dk.
Novozymes (Denmark) · DKAarhus University · DKAlbumedix (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Albumin is the most abundant plasma protein involved in the transport of many compounds, such as fatty acids, bilirubin, and heme. The endothelial cellular neonatal Fc receptor (FcRn) has been suggested to play a central role in maintaining high albumin plasma levels through a cellular recycling pathway. However, direct mapping of this process is still lacking. This work presents the use of wild-type and engineered recombinant albumins with either decreased or increased FcRn affinity in combination with a low or high FcRn-expressing endothelium cell line to clearly define the FcRn involvement, intracellular pathway, and kinetics of albumin trafficking by flow cytometry, quantitative confocal microscopy, and an albumin-recycling assay. We found that cellular albumin internalization was proportional to FcRn expression and albumin-binding affinity. Albumin accumulation in early endosomes was independent of FcRn-binding affinity, but differences in FcRn-binding affinities significantly affected the albumin distribution between late endosomes and lysosomes. Unlike albumin with low FcRn-binding affinity, albumin with high FcRn-binding affinity was directed less to the lysosomes, suggestive of FcRn-directed albumin salvage from lysosomal degradation. Furthermore, the amount of recycled albumin in cell culture media corresponded to FcRn-binding affinity, with a ∼3.3-fold increase after 1 h for the high FcRn-binding albumin variant compared with wild-type albumin. Together, these findings uncover an FcRn-dependent endosomal cellular-sorting pathway that has great importance in describing fundamental mechanisms of intracellular albumin recycling and the possibility to tune albumin-based therapeutic effects by FcRn-binding affinity.

Indexed as

Amino Acid SubstitutionCell Line, TransformedElectron Probe MicroanalysisEndosomesEndothelium, VascularFluorescent DyesGene Expression RegulationGenetic VariationGreen Fluorescent ProteinsHistocompatibility Antigens Class IHumansHydrogen-Ion ConcentrationIodine RadioisotopesKineticsLysosomesMicroscopy, ConfocalFc receptor, neonatalFluorescent DyesGreen Fluorescent ProteinsHistocompatibility Antigens Class IIodine RadioisotopesReceptors, FcRecombinant Fusion ProteinsRecombinant ProteinsSerum Albuminalbumincellular recyclingendosomeFc receptorintracellular processingintracellular traffickingreceptor recycling

Identifiers

PMID28637874
PMCPMC5555191
OpenAlexW2980750880

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.