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Updated: Apr 22, 2026

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Proximity Labeling Reveals How Lrp2 Interacts with the Endocytic Machine.

Tian H Shen1, Andrew Beenken1, Hediye Erdjument-Bromage2

  • 1Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York 10032, United States.

Journal of Proteome Research
|April 20, 2026
PubMed
Summary
This summary is machine-generated.

Low-density lipoprotein-related receptor 2 (LRP2) is crucial for kidney endocytosis beyond nutrient uptake. This study reveals LRP2 organizes apical membranes and interacts with key endocytic regulators, essential for kidney function.

Keywords:
APEX2Lrp2Megalinproximity biotinylationproximity labeling

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Nephrology

Background:

  • Low-density lipoprotein-related receptor 2 (LRP2), also known as Megalin, is a scavenger receptor involved in nutrient and toxin reabsorption in the kidney.
  • LRP2, along with Cubilin and Amnionless, mediates endocytosis of various ligands from glomerular filtrate.
  • Emerging evidence suggests LRP2 has roles in endocytosis beyond its known ligand-binding functions.

Purpose of the Study:

  • To elucidate the broader role of LRP2 in endocytosis.
  • To identify LRP2's interacting partners involved in endocytic processes.
  • To understand how LRP2 organizes cellular machinery at the apical membrane.

Main Methods:

  • Engineered LRP2-APEX2-expressing mice for in vivo proximity-dependent biotinylation.
  • Utilized mass spectrometry to identify biotinylated cytoplasmic proteins interacting with LRP2.
  • Performed kidney tissue immunostaining to validate protein localization and interactions.

Main Results:

  • Identified known and novel endocytic regulators interacting with LRP2.
  • Demonstrated LRP2's role in organizing apical membrane proteins via PDZ domain interactions.
  • Showcased LRP2's engagement with molecular motors and regulators during endocytosis.

Conclusions:

  • LRP2 plays a central role in organizing the apical membrane and facilitating endocytosis.
  • LRP2 interacts with a network of proteins critical for kidney reabsorption and fluid-phase endocytosis.
  • These interactions are dependent on the presence of LRP2, highlighting its essential function.