ArticleMolecular biology of the cell2004
Elevated endosomal cholesterol levels in Niemann-Pick cells inhibit rab4 and perturb membrane recycling.
Article in Molecular biology of the cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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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.
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.
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Who cites it
65 citing papers in PubMed, 137 citations in OpenAlex.
- Proteomics of specific treatment-related alterations in Fabry disease: a strategy to identify biological abnormalities.Proceedings of the National Academy of Sciences of the United States of America · 2007Trial
- Endosome Traffic Modulates Pro-Inflammatory Signal Transduction in CD4International journal of molecular sciences · 2023Review
- Linking Late Endosomal Cholesterol with Cancer Progression and Anticancer Drug Resistance.International journal of molecular sciences · 2022Review
- Sphingomyelinases and Liver Diseases.Biomolecules · 2020Review
- 2-Hydroxypropyl-gamma-cyclodextrin overcomes NPC1 deficiency by enhancing lysosome-ER association and autophagy.Scientific reports · 2020Article
- Making a Dent in Dent Disease.Function (Oxford, England) · 2020Review
- LRRK2-Related Parkinson's Disease Due to Altered Endolysosomal Biology With Variable Lewy Body Pathology: A Hypothesis.Frontiers in neuroscience · 2020Review
- Exosome Production Is Key to Neuronal Endosomal Pathway Integrity in Neurodegenerative Diseases.Frontiers in neuroscience · 2019Review
- Apolipoprotein E4 genotype compromises brain exosome production.Brain : a journal of neurology · 2019Article
- Alterations in Cellular Processes Involving Vesicular Trafficking and Implications in Drug Delivery.Biomimetics (Basel, Switzerland) · 2018Review
- The recycling endosome and bacterial pathogens.Cellular microbiology · 2018Review
- Regulation of the Cell Biology of Antigen Cross-Presentation.Annual review of immunology · 2018Review
- Conserved Oligomeric Golgi and Neuronal Vesicular Trafficking.Handbook of experimental pharmacology · 2018Review
- Recent neuroimaging, neurophysiological, and neuropathological advances for the understanding of NPC.F1000Research · 2018Review
- Lipid metabolism fattens up hedgehog signaling.BMC biology · 2017Review
- Histone deacetylase inhibitors correct the cholesterol storage defect in most Niemann-Pick C1 mutant cells.Journal of lipid research · 2017Article
- Domain 4 (D4) of Perfringolysin O to Visualize Cholesterol in Cellular Membranes-The Update.Sensors (Basel, Switzerland) · 2017Review
- Lipids, lysosomes, and autophagy.Journal of lipid research · 2016Review
- The comings and goings of MHC class I molecules herald a new dawn in cross-presentation.Immunological reviews · 2016Review
- Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In normal human skin fibroblasts (HSFs), fluorescent glycosphingolipid analogues are endocytosed and sorted into two pools, one that is recycled to the plasma membrane and one that is transported to the Golgi complex. Here, we investigated glycosphingolipid recycling in Niemann-Pick type A and C lipid storage disease fibroblasts (NPFs). Cells were incubated with a fluorescent analogue of lactosylceramide (LacCer) at 16 degrees C to label early endosomes (EEs), shifted to 37 degrees C, and lipid recycling was quantified. Using dominant negative rabs, we showed that, in normal HSFs, LacCer recycling was rapid (t1/2 approximately 8 min) and mainly rab4-dependent. In NPFs, LacCer recycling was delayed (t1/2 approximately 30-40 min), and rab4-dependent recycling was absent, whereas rab11-dependent recycling predominated. Transferrin recycling via the rab4 pathway was similarly perturbed in NPFs. Compared with normal HSFs, EEs in NPFs showed high cholesterol levels and an altered organization of rab4. In vitro extraction of rab4 (but not rab11) with GDP dissociation inhibitor was severely attenuated in NPF endosomal fractions. This impairment was reversed with cholesterol depletion of isolated endosomes or with high-salt treatment of endosomes. These data suggest that abnormal membrane recycling in NPFs results from specific inhibition of rab4 function by excess cholesterol in EEs.
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Registered trials
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.