Evidence map›Paper›PMID 23038769›Full record

ArticleJournal of cell science2012

Mechanism of polarized lysosome exocytosis in epithelial cells.

Jin Xu, Kimberly A Toops, Fernando Diaz, Jose Maria Carvajal-Gonzalez, Diego Gravotta, Francesca Mazzoni, Ryan Schreiner, Enrique Rodriguez-Boulan, Aparna Lakkaraju

Erratum issuedAbstract read
In one paragraph

Article in Journal of cell science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

31 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Early Endosomes Act as Local Exocytosis Hubs to Repair Endothelial Membrane Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  6. Article
  7. Spatial organization of lysosomal exocytosis relies on membrane tension gradients.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. The cell biology of the retinal pigment epithelium.Progress in retinal and eye research · 2020
    Review
  13. Intracellular Transport in Cancer Metabolic Reprogramming.Frontiers in cell and developmental biology · 2020
    Review
  14. Article
  15. Article
  16. Article
  17. Alveolar epithelial cell processing of nanoparticles activates autophagy and lysosomal exocytosis.American journal of physiology. Lung cellular and molecular physiology · 2018
    Article
  18. Article
  19. Article
  20. Protective responses to sublytic complement in the retinal pigment epithelium.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Jin XuDepartment of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Kimberly A Toops
Fernando Diaz
Jose Maria Carvajal-Gonzalez
Diego Gravotta
Francesca Mazzoni
Ryan Schreiner
Enrique Rodriguez-Boulan
Aparna Lakkaraju
Cornell University · USUniversity of Wisconsin–Madison · US

Funding

RETINA--REVERSED POLARITY IN RPER01EY008538 · NEI · WEILL MEDICAL COLL OF CORNELL UNIV · PI RODRIGUEZ-BOULAN, ENRIQUE J · 1991 to 2020
$13.4M
UW Vision Research Core - Administrative CoreP30EY016665 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI ROBERT W NICKELLS · 2005 to 2026
$12.6M
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 EY08538NEI NIH HHS P30 EY016665NEI NIH HHS P30EY016665NEI NIH HHS R01 EY008538NIGMS NIH HHS R01 GM034107
6 · The paper itself

Abstract

Fusion of lysosomes with the plasma membrane is a calcium-dependent process that is crucial for membrane repair, limiting pathogen entry and clearing cellular debris. In non-polarized cells, lysosome exocytosis facilitates rapid resealing of torn membranes. Here, we investigate the mechanism of lysosome exocytosis in polarized epithelia, the main barrier between the organism and the external environment and the first line of defense against pathogens. We find that in polarized Madin-Darby canine kidney (MDCK) cells, calcium ionophores or pore-forming toxins cause lysosomes to fuse predominantly with the basolateral membrane. This polarized exocytosis is regulated by the actin cytoskeleton, membrane cholesterol and the clathrin adaptor AP-1. Depolymerization of actin, but not microtubules, causes apical lysosome fusion, supporting the hypothesis that cortical actin is a barrier to exocytosis. Overloading lysosomes with cholesterol inhibits exocytosis, suggesting that excess cholesterol paralyzes lysosomal traffic. The clathrin adaptor AP-1 is responsible for accurately targeting syntaxin 4 to the basolateral domain. In cells lacking either the ubiquitous AP-1A or the epithelial-specific AP-1B, syntaxin 4 is non-polar. This causes lysosomes to fuse with both the apical and basolateral membranes. Consistent with these findings, RNAi-mediated depletion of syntaxin 4 inhibits basolateral exocytosis in wild-type MDCK, and both apical and basolateral exocytosis in cells lacking AP-1A or AP-1B. Our results provide fundamental insight into the molecular machinery involved in membrane repair in polarized epithelia and suggest that AP-1 is a crucial regulator of this process.

Indexed as

ActinsAdaptor Protein Complex 1AnimalsCalciumCholesterolDogsEpithelial CellsExocytosisLysosomesMadin Darby Canine Kidney CellsActinsAdaptor Protein Complex 1CalciumCholesterol

Identifiers

PMID23038769
PMCPMC3585513
OpenAlexW2067384557

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.