Evidence map›Paper›PMID 14528014›Full record

ArticleMolecular biology of the cell2003

The adaptor protein ARH escorts megalin to and through endosomes.

Masaaki Nagai, Timo Meerloo, Tetsuro Takeda, Marilyn Gist Farquhar

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

45 citing papers in PubMed, 101 citations in OpenAlex.

  1. Megalin: from structure to function.Nature reviews. Nephrology · 2026
    Review
  2. Review
  3. Article
  4. Vacuolar HJournal of cellular physiology · 2025
    Article
  5. Efficient and selective kidney targeting by chemically modified carbohydrate conjugates.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. The Journal of biological chemistry · 2018
    Article
  15. Article
  16. Endocytic receptor LRP2/megalin-of holoprosencephaly and renal Fanconi syndrome.Pflugers Archiv : European journal of physiology · 2017
    Review
  17. Review
  18. Subcellular Trafficking of Mammalian Lysosomal Proteins: An Extended View.International journal of molecular sciences · 2016
    Review
  19. Megalin Is Predominantly Observed in Vesicular Structures in First and Third Trimester Cytotrophoblasts of the Human Placenta.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2016
    Article
  20. 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

4 authors at 1 institution in 1 country.

Masaaki NagaiDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Timo Meerloo
Tetsuro Takeda
Marilyn Gist Farquhar
University of California San Diego · US

Funding

GLOMERULAR CAPILLARIES--NORMAL &PATHOLOGICR01DK017724 · NIDDK · YALE UNIVERSITY · PI FARQUHAR, MARILYN GIST · 1986 to 2008
$3.6M
Glomerular Capillaries-- Normal and PathologicR37DK017724 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FARQUHAR, MARILYN GIST · 2009 to 2015
$2.7M
NIDDK NIH HHS DK17724NIDDK NIH HHS R01 DK017724NIDDK NIH HHS R37 DK017724
6 · The paper itself

Abstract

Megalin is an endocytic receptor that binds multiple ligands and is essential for many physiological processes such as brain development and uptake of proteins by the kidney tubule, yolk sac, and thyroid. The cytoplasmic tail of megalin contains two FXNPXY motifs. Autosomal recessive hypercholesterolemia (ARH) is an adaptor protein that binds to the FXNPXY motif of the low-density lipoprotein receptor as well as clathrin and AP-2. We found that ARH also binds to the first FXNPXY motif of megalin in two-hybrid, pull-down and coimmunoprecipitation assays. ARH colocalizes with megalin in clathrin coated pits and in recycling endosomes in the Golgi region. When cells are treated with nocodazole, the recycling endosomes containing megalin and ARH disperse. On internalization of megalin, ARH and megalin are first seen in clathrin coated pits followed by sequential localization in early endosomes and tubular recycling endosomes in the pericentriolar region followed by their reappearance at the cell surface. Expression of ARH in Madin-Darby canine kidney cells expressing megalin mini-receptors enhances megalin-mediated uptake of 125I-lactoferrin, a megalin ligand. These results show that ARH facilitates endocytosis of megalin, escorts megalin along its endocytic route and raise the possibility that transport through the endosomal system is selective and requires interaction with specific adaptor proteins.

Indexed as

Adaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAmino Acid SequenceAnimalsCell MembraneCells, CulturedCloning, MolecularCOP-Coated VesiclesDogsEndocytosisEndosomesGolgi ApparatusHumansLactoferrinLow Density Lipoprotein Receptor-Related Protein-2Microscopy, ImmunoelectronAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportLactoferrinLDLRAP1 protein, humanLow Density Lipoprotein Receptor-Related Protein-2Nocodazole

Identifiers

PMID14528014
PMCPMC284800
OpenAlexW2052648526

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.