Evidence map›Paper›PMID 37126375›Full record

ArticleMolecular biology of the cell2023

Megalin, cubilin, and Dab2 drive endocytic flux in kidney proximal tubule cells.

Youssef Rbaibi, Kimberly R Long, Katherine E Shipman, Qidong Ren, Catherine J Baty, Ossama B Kashlan, Ora A Weisz

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
5.6field-weighted citation impact, top 4% 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

25 citing papers in PubMed, 27 citations in OpenAlex.

  1. Megalin: from structure to function.Nature reviews. Nephrology · 2026
    Review
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  17. Spns1 is an iron transporter essential for megalin-dependent endocytosis.American journal of physiology. Renal physiology · 2024
    Article
  18. Article
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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

7 authors at 2 institutions in 2 countries.

Youssef RbaibiRenal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
Kimberly R LongRenal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
Katherine E ShipmanRenal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
Qidong RenSchool of Medicine, Tsinghua University, Beijing, China, 100084.
Catherine J BatyRenal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
Ossama B KashlanRenal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
Ora A WeiszRenal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
University of Pittsburgh · USTsinghua University · CN

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
Endocytic Pathway Dysfunction in Dent DiseaseR01DK125049 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WEISZ, ORA A · 2020 to 2024
$2.3M
Proximal tubule endocytosis in normal and nephrotic kidneysR01DK118726 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WEISZ, ORA A · 2019 to 2022
$1.8M
Leica Stellaris Confocal for Kidney Imaging CoreS10OD028596 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI APODACA, GERARD L · 2021 to 2021
$596k
Integrated perfusion and confocal imaging systemS10OD021627 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WEISZ, ORA A · 2016 to 2016
$479k
Megalin Traffic in Dent DiseaseF31DK121394 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHIPMAN, KATHERINE E · 2019 to 2021
$93k
NCI NIH HHS P30 CA047904NIDDK NIH HHS F31 DK121394NIDDK NIH HHS P30 DK079307NIDDK NIH HHS R01 DK118726NIDDK NIH HHS R01 DK125049NIH HHS S10 OD021627NIH HHS S10 OD028596
6 · The paper itself

Abstract

The kidney proximal tubule (PT) elaborates a uniquely high-capacity apical endocytic pathway to retrieve albumin and other proteins that escape the glomerular filtration barrier. Megalin and cubilin/amnionless (CUBAM) receptors engage Dab2 in these cells to mediate clathrin-dependent uptake of filtered ligands. Knockout of megalin or Dab2 profoundly inhibits apical endocytosis and is believed to atrophy the endocytic pathway. We generated CRISPR/Cas9 knockout (KO) clones lacking cubilin, megalin, or Dab2 expression in highly differentiated PT cells and determined the impact on albumin internalization and endocytic pathway function. KO of each component had different effects on the concentration dependence of albumin uptake as well its distribution within PT cells. Reduced uptake of a fluid phase marker was also observed, with megalin KO cells having the most dramatic decline. Surprisingly, protein levels and distribution of key endocytic proteins were preserved in KO PT cell lines and in megalin KO mice, despite the reduced endocytic activity. Our data highlight specific functions of megalin, cubilin, and Dab2 in apical endocytosis and demonstrate that these proteins drive endocytic flux without compromising the physical integrity of the apical endocytic pathway. Our studies suggest a novel model to explain how these components coordinate endocytic uptake in PT cells.

Indexed as

Low Density Lipoprotein Receptor-Related Protein-2Receptors, Cell SurfaceAdaptor Proteins, Signal TransducingAlbuminsAnimalsApoptosis Regulatory ProteinsEndocytosisKidney Tubules, ProximalMiceMice, KnockoutAdaptor Proteins, Signal TransducingAlbuminsApoptosis Regulatory ProteinsDab2 protein, mouseintrinsic factor-cobalamin receptorLow Density Lipoprotein Receptor-Related Protein-2Lrp2 protein, mouseReceptors, Cell Surface

Identifiers

PMID37126375
PMCPMC10295476
OpenAlexW4367049933

What OpenQuestion holds

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LicenceCC BY-NC-SA
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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.