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The Early Endosome: Endocytosis of Transferrin01:28

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Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
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Related Experiment Video

Updated: Feb 8, 2026

The Participant-Reported Implementation Update and Score PRIUS: A Novel Method for Capturing Implementation-Related Data Over Time
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Transferrin and transferrin receptors update.

Hiroshi Kawabata1

  • 1Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa-ken 920-0293, Japan.

Free Radical Biology & Medicine
|July 4, 2018
PubMed
Summary

Transferrin (Tf) and its receptors (TfR1 and TfR2) are crucial for iron delivery and cellular uptake in vertebrates. Understanding TfR2

Keywords:
Erythropoietin receptorFerritinHepcidinHereditary hemochromatosisTransferrinTransferrin receptor 1Transferrin receptor 2

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Hematology

Background:

  • Transferrin (Tf) is the primary iron transporter in vertebrate circulation.
  • Tf receptor 1 (TfR1) mediates cellular iron uptake and serves as an entry point for pathogens like arenaviruses and Plasmodium vivax.
  • Tf receptor 2 (TfR2) is involved in iron sensing, erythropoiesis, and iron transport within cells.

Purpose of the Study:

  • To review and summarize current knowledge on mammalian transferrin (Tf) and its receptors.
  • To highlight the diverse roles of TfR1 and TfR2 in iron metabolism and cellular processes.
  • To discuss the clinical implications of Tf and its receptors in various diseases.

Main Methods:

  • Literature review of mammalian Tf and its receptors.
  • Analysis of TfR1 and TfR2 functions in iron uptake, cellular signaling, and disease pathogenesis.
  • Summary of therapeutic strategies involving apo-Tf.

Main Results:

  • TfR1 mediates cellular uptake of Tf-bound iron and is a viral/parasitic entry receptor.
  • TfR2 plays a key role in hepatocyte iron sensing, erythropoiesis regulation, and intracellular iron transport.
  • Defects in TfR2 are linked to hereditary hemochromatosis due to hepcidin dysregulation.
  • Apo-Tf shows therapeutic potential for iron overload, anemia, and ischemic conditions.

Conclusions:

  • Mammalian Tf and its receptors, TfR1 and TfR2, are central to iron homeostasis and cellular function.
  • TfR2's multifaceted roles in iron sensing and erythropoiesis underscore its importance in health and disease.
  • Further research into Tf and its receptors may lead to novel therapeutic interventions for iron-related disorders.