ArticleNature communications2020
A trimeric Rab7 GEF controls NPC1-dependent lysosomal cholesterol export.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.
What it found
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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
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 100 citations in OpenAlex.
- Association between blood lipid levels and risk of gastric cancer: A systematic review and meta-analysis.PloS one · 2023Pooled it
- Cholesterol homeostasis and cancer: a new perspective on the low-density lipoprotein receptor.Cellular oncology (Dordrecht, Netherlands) · 2022Pooled it
- Small Molecules to Elevate Rab7-GTPase Activity and Lower Cholesterol Accumulation in Niemann-Pick Type C Disease.Pharmaceutical research · 2026Article
- AI-guided multi-omics analysis identifies NPC1-modulated susceptibility to SARS-CoV-2 infection under PMNature communications · 2026Article
- A graph-based learning approach to predict the effects of gene perturbations on molecular phenotypes.bioRxiv : the preprint server for biology · 2026Article
- Unraveling Lysosomal Exocytosis: From Molecular Mechanisms to Physiological Functions.Traffic (Copenhagen, Denmark) · 2026Review
- Review of methods for the determination of cellular cholesterol content: principles, advantages, limitations, applications, and perspectives.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2025Review
- ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver.Communications biology · 2025Article
- Cryo-EM structure of the human MON1A-CCZ1-RAB7A complex provides insights into nucleotide exchange mechanism.Life metabolism · 2025Article
- Endosome maturation during ER stress relies on the ubiquitin-binding domain of histone deacetylase 6.Molecular biology of the cell · 2025Article
- Population-scale gene-based analysis of whole-genome sequencing provides insights into metabolic health.Nature genetics · 2025Article
- Proteomic Profiling of Extracellular Vesicles Distinguishes Prostate Cancer Molecular Subtypes.Journal of extracellular vesicles · 2025Article
- Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned.Science advances · 2025Article
- The health impacts and genetic architecture of food liking in cardio-metabolic diseases.Nature communications · 2025Article
- ESCRTing the RABs through conversion.Biochemical Society transactions · 2025Review
- Systematic interrogation of functional genes underlying cholesterol and lipid homeostasis.Genome biology · 2025Article
- Endosomal trafficking participates in lipid droplet catabolism to maintain lipid homeostasis.Nature communications · 2025Article
- Unifying biology of neurodegeneration in lysosomal storage diseases.Journal of inherited metabolic disease · 2025Review
- TPC2: From Blond Hair to Melanoma?Cancers · 2024Review
- Spatiotemporal recruitment of the ubiquitin-specific protease USP8 directs endosome maturation.eLife · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Cholesterol import in mammalian cells is mediated by the LDL receptor pathway. Here, we perform a genome-wide CRISPR screen using an endogenous cholesterol reporter and identify >100 genes involved in LDL-cholesterol import. We characterise C18orf8 as a core subunit of the mammalian Mon1-Ccz1 guanidine exchange factor (GEF) for Rab7, required for complex stability and function. C18orf8-deficient cells lack Rab7 activation and show severe defects in late endosome morphology and endosomal LDL trafficking, resulting in cellular cholesterol deficiency. Unexpectedly, free cholesterol accumulates within swollen lysosomes, suggesting a critical defect in lysosomal cholesterol export. We find that active Rab7 interacts with the NPC1 cholesterol transporter and licenses lysosomal cholesterol export. This process is abolished in C18orf8-, Ccz1- and Mon1A/B-deficient cells and restored by a constitutively active Rab7. The trimeric Mon1-Ccz1-C18orf8 (MCC) GEF therefore plays a central role in cellular cholesterol homeostasis coordinating Rab7 activation, endosomal LDL trafficking and NPC1-dependent lysosomal cholesterol export.
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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.