ArticleeLife2020
Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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.
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.
Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Soma to neuron communication links stress adaptation to stress avoidance behavior.bioRxiv : the preprint server for biology · 2025Article
- Niemann Pick C1 mistargeting disrupts lysosomal cholesterol homeostasis contributing to neurodegeneration in a Batten disease model.Science advances · 2025Article
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- Investigating p.Ala1035Val in NPC1: New Cellular Models for Niemann-Pick Type C Disease.International journal of molecular sciences · 2024Article
- Conformational changes in the Niemann-Pick type C1 protein NCR1 drive sterol translocation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Binding of Cholesterol to the N-Terminal Domain of the NPC1L1 Transporter: Analysis of the Epimerization-Related Binding Selectivity and Loop Mutations.Journal of chemical information and modeling · 2024Article
- Analysis of cis-regulatory changes underlying phenotype divergence shaped by domestication in pigs.Frontiers in genetics · 2024Article
- The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease.Nature reviews. Molecular cell biology · 2023Review
- Lysosome-targeted multifunctional lipid probes reveal the sterol transporter NPC1 as a sphingosine interactor.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Cerebellum in Niemann-Pick C1 Disease: Mouse Versus Man.Cerebellum (London, England) · 2023Review
- The Antifungal Antibiotic Filipin as a Diagnostic Tool of Cholesterol Alterations in Lysosomal Storage Diseases and Neurodegenerative Disorders.Antibiotics (Basel, Switzerland) · 2023Review
- Peroxisomal defects in microglial cells induce a disease-associated microglial signature.Frontiers in molecular neuroscience · 2023Article
- CRISPR screens for lipid regulators reveal a role for ER-bound SNX13 in lysosomal cholesterol export.The Journal of cell biology · 2022Article
- Proteomic analysis of s-acylated proteins in human retinal pigment epithelial cells and the role of palmitoylation of Niemann-Pick type C1 protein in cholesterol transport.Frontiers in aging neuroscience · 2022Article
- Structures of dimeric human NPC1L1 provide insight into mechanisms for cholesterol absorption.Science advances · 2021Article
- Structural insights into the mechanism of human NPC1L1-mediated cholesterol uptake.Science advances · 2021Article
- Inhibition of Histone Deacetylases 1, 2, and 3 Enhances Clearance of Cholesterol Accumulation in Niemann-Pick C1 Fibroblasts.ACS pharmacology & translational science · 2021Article
- TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine.The Journal of cell biology · 2021Article
- Molecular dynamics study with mutation shows that N-terminal domain structural re-orientation in Niemann-Pick type C1 is required for proper alignment of cholesterol transport.Journal of neurochemistry · 2021Article
- Genetic defects in the sphingolipid degradation pathway and their effects on microglia in neurodegenerative disease.Cellular signalling · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Transport of LDL-derived cholesterol from lysosomes into the cytoplasm requires NPC1 protein; NPC1L1 mediates uptake of dietary cholesterol. We introduced single disulfide bonds into NPC1 and NPC1L1 to explore the importance of inter-domain dynamics in cholesterol transport. Using a sensitive method to monitor lysosomal cholesterol efflux, we found that NPC1's N-terminal domain need not release from the rest of the protein for efficient cholesterol export. Either introducing single disulfide bonds to constrain lumenal/extracellular domains or shortening a cytoplasmic loop abolishes transport activity by both NPC1 and NPC1L1. The widely prescribed cholesterol uptake inhibitor, ezetimibe, blocks NPC1L1; we show that residues that lie at the interface between NPC1L1's three extracellular domains comprise the drug's binding site. These data support a model in which cholesterol passes through the cores of NPC1/NPC1L1 proteins; concerted movement of various domains is needed for transfer and ezetimibe blocks transport by binding to multiple domains simultaneously.
Indexed as
Identifiers
What OpenQuestion holds
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.