Evidence map›Paper›PMID 23733943›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Abnormal accumulation and recycling of glycoproteins visualized in Niemann-Pick type C cells using the chemical reporter strategy.

Ngalle Eric Mbua, Heather Flanagan-Steet, Steven Johnson, Margreet A Wolfert, Geert-Jan Boons, Richard Steet

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Alterations in Proteostasis Mechanisms in Niemann-Pick Type C Disease.International journal of molecular sciences · 2024
    Review
  3. Cracking the "Sugar Code": A Snapshot ofFrontiers in plant science · 2021
    Review
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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

6 authors at 2 institutions in 2 countries.

Ngalle Eric MbuaDepartment of Chemistry, University of Georgia, Athens, GA 30602, USA.
Heather Flanagan-Steet
Steven Johnson
Margreet A Wolfert
Geert-Jan Boons
Richard Steet
Carbohydrate Competence Center · NLUniversity of Georgia · US

Funding

ZINC DEFICIENCY &PROTEIN EXPRESSION IN RAT OLFACTORY BULBSP41RR005351 · NCRR · UNIVERSITY OF GEORGIA (UGA) · PI VENOT, ANDRE · 1989 to 2011
$18.4M
TR&D3. Approaches to Proteoglycan Function at Biochemical and Cellular LevelsP41GM103390 · NIGMS · UNIVERSITY OF GEORGIA · PI MOREMEN, KELLEY W. · 2012 to 2019
$14.5M
PATHOGENIC MECHANISMS OF LYSOSOMAL DISEASER01GM086524 · NIGMS · UNIVERSITY OF GEORGIA · PI STEET, RICHARD · 2009 to 2021
$4.0M
NCRR NIH HHS P41 RR005351NCRR NIH HHS P41RR05351NIGMS NIH HHS 8P41GM103390NIGMS NIH HHS P41 GM103390NIGMS NIH HHS R01 GM086524
6 · The paper itself

Abstract

Niemann-Pick type C (NPC) disease is characterized by impaired cholesterol efflux from late endosomes and lysosomes and secondary accumulation of lipids. Although impaired trafficking of individual glycoproteins and glycolipids has been noted in NPC cells and other storage disorders, there is currently no effective way to monitor their localization and movement en masse. Using a chemical reporter strategy in combination with pharmacologic treatments, we demonstrate a disease-specific and previously unrecognized accumulation of a diverse set of glycoconjugates in NPC1-null and NPC2-deficient fibroblasts within endocytic compartments. These labeled vesicles do not colocalize with the cholesterol-laden compartments of NPC cells. Experiments using the endocytic uptake marker dextran show that the endosomal accumulation of sialylated molecules can be largely attributed to impaired recycling as opposed to altered fusion of vesicles. Treatment of either NPC1-null or NPC2-deficient cells with cyclodextrin was effective in reducing cholesterol storage as well as the endocytic accumulation of sialoglycoproteins, demonstrating a direct link between cholesterol storage and abnormal recycling. Our data further demonstrate that this accumulation is largely glycoproteins, given that inhibitors of O-glycan initiation or N-glycan processing led to a significant reduction in staining intensity. Taken together, our results provide a unique perspective on the trafficking defects in NPC cells, and highlight the utility of this methodology in analyzing cells with altered recycling and turnover of glycoproteins.

Indexed as

Azidesbeta-CyclodextrinsCarrier ProteinsCell LineCholesterolDextransEndosomesFibroblastsGalactosamineGlycoconjugatesGlycoproteinsHumansIntracellular Signaling Peptides and ProteinsLysosomesMembrane GlycoproteinsNiemann-Pick C1 ProteinAzidesbeta-CyclodextrinsCarrier ProteinsCholesterolDextransGalactosamineGlycoconjugatesGlycoproteinsIntracellular Signaling Peptides and ProteinsMembrane Glycoproteinsmethyl-beta-cyclodextrinNiemann-Pick C1 ProteinNPC1 protein, humanNPC2 protein, humanSialoglycoproteinsVesicular Transport Proteins

Identifiers

PMID23733943
PMCPMC3690855
OpenAlexW2041465346

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.