Evidence map›Paper›PMID 31091172›Full record

ArticleMolecular biology of the cell2019

Clathrin and clathrin adaptor AP-1 control apical trafficking of megalin in the biosynthetic and recycling routes.

Diego Gravotta, Andres Perez Bay, Caspar T H Jonker, Patrick J Zager, Ignacio Benedicto, Ryan Schreiner, Paulo S Caceres, Enrique Rodriguez-Boulan

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.2field-weighted citation impact, top 14% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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  6. Cells · 2023
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  7. Human epiblast lumenogenesis: From a cell aggregate to a lumenal cyst.Seminars in cell & developmental biology · 2022
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  8. Article
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  11. Review
  12. Article
  13. Membrane Lipids in Epithelial Polarity: Sorting out the PIPs.Frontiers in cell and developmental biology · 2022
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. 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 1 institution in 1 country.

Diego GravottaMargaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY 10065.
Andres Perez BayMargaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY 10065.
Caspar T H JonkerMargaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY 10065.
Patrick J ZagerMargaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY 10065.
Ignacio BenedictoMargaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY 10065.
Ryan SchreinerMargaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY 10065.
Paulo S CaceresMargaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY 10065.
Enrique Rodriguez-BoulanMargaret Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY 10065.
Cornell University · US

Funding

RETINA--REVERSED POLARITY IN RPER01EY008538 · NEI · WEILL MEDICAL COLL OF CORNELL UNIV · PI RODRIGUEZ-BOULAN, ENRIQUE J · 1991 to 2020
$13.4M
SORTING OF PLASMA MEMBRANE PROTEINS IN EPITHELIAL CELLSR01GM034107 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI RODRIGUEZ-BOULAN, ENRIQUE J · 1985 to 2019
$9.6M
NEI NIH HHS R01 EY008538NIGMS NIH HHS R01 GM034107
6 · The paper itself

Abstract

Megalin (gp330, LRP-2) is a protein structurally related to the low-density lipoprotein receptor family that displays a large luminal domain with multiligand binding properties. Megalin localizes to the apical surface of multiple epithelia, where it participates in endocytosis of a variety of ligands performing roles important for development or homeostasis. We recently described the apical recycling pathway of megalin in Madin-Darby canine kidney (MDCK) cells and found that it is a long-lived, fast recycling receptor with a recycling turnover of 15 min and a half-life of 4.8 h. Previous work implicated clathrin and clathrin adaptors in the polarized trafficking of fast recycling basolateral receptors. Hence, here we study the role of clathrin and clathrin adaptors in megalin's apical localization and trafficking. Targeted silencing of clathrin or the γ1 subunit of clathrin adaptor AP-1 by RNA interference in MDCK cells disrupted apical localization of megalin, causing its redistribution to the basolateral membrane. In contrast, silencing of the γ2 subunit of AP-1 had no effect on megalin polarity. Trafficking assays we developed using FM4-HA-miniMegalin-GFP, a reversible conditional endoplasmic reticulum-retained chimera, revealed that clathrin and AP-1 silencing disrupted apical sorting of megalin in both biosynthetic and recycling routes. Our experiments demonstrate that clathrin and AP-1 control the sorting of an apical transmembrane protein.

Indexed as

EndocytosisAdaptor Protein Complex 1AnimalsClathrinDogsGreen Fluorescent ProteinsIntegrin beta3Low Density Lipoprotein Receptor-Related Protein-2Madin Darby Canine Kidney CellsProtein SubunitsQa-SNARE ProteinsAdaptor Protein Complex 1ClathrinGreen Fluorescent ProteinsIntegrin beta3Low Density Lipoprotein Receptor-Related Protein-2Protein SubunitsQa-SNARE Proteins

Identifiers

PMID31091172
PMCPMC6727755
OpenAlexW2945787236

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.