ArticlePLoS genetics2010
Multivesicular body formation requires OSBP-related proteins and cholesterol.
Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 67 citations in OpenAlex.
- The ER-Golgi Lipid Exchanger PsORP1 Is Essential for Phytophthora sojae Development and Is Blocked by Oxathiapiprolin via Its OSBP-Related Domain (ORD).Molecular plant pathology · 2026Article
- Lactobacillus paragasseri ameliorates age-dependent thermotaxis decline in Caenorhabditis elegans.Scientific reports · 2026Article
- Intracellular Cholesterol Trafficking.Cold Spring Harbor perspectives in biology · 2023Review
- Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2023Review
- Article
- Up-regulation of Osh6 boosts an anti-aging membrane trafficking pathway toward vacuoles.Microbial cell (Graz, Austria) · 2022Article
- Linking Late Endosomal Cholesterol with Cancer Progression and Anticancer Drug Resistance.International journal of molecular sciences · 2022Review
- Article
- Caenorhabditis elegans junctophilin has tissue-specific functions and regulates neurotransmission with extended-synaptotagmin.Genetics · 2021Article
- Endosomal Cholesterol in Viral Infections - A Common Denominator?Frontiers in physiology · 2021Review
- Adenovirus Reveals New Pathway for Cholesterol Egress from the Endolysosomal System.International journal of molecular sciences · 2020Review
- Lipid Transfer-Dependent Endosome Maturation Mediated by Protrudin and PDZD8 in Neurons.Frontiers in cell and developmental biology · 2020Review
- Prominin2 Drives Ferroptosis Resistance by Stimulating Iron Export.Developmental cell · 2019Article
- Osh Proteins Control Nanoscale Lipid Organization Necessary for PI(4,5)PMolecular cell · 2019Article
- Expanded genetic screening ineLife · 2018Article
- Bridging the molecular and biological functions of the oxysterol-binding protein family.Cellular and molecular life sciences : CMLS · 2018Review
- Membrane dynamics and organelle biogenesis-lipid pipelines and vesicular carriers.BMC biology · 2017Article
- The role of exosomes in the pathogenesis of Alzheimer' disease.Translational neurodegeneration · 2017Review
- Interactions between the Coxiella burnetii parasitophorous vacuole and the endoplasmic reticulum involve the host protein ORP1L.Cellular microbiology · 2017Article
- Regulation of calcium and phosphoinositides at endoplasmic reticulum-membrane junctions.Biochemical Society transactions · 2016Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In eukaryotes, different subcellular organelles have distinct cholesterol concentrations, which is thought to be critical for biological functions. Oxysterol-binding protein-related proteins (ORPs) have been assumed to mediate nonvesicular cholesterol trafficking in cells; however, their in vivo functions and therefore the biological significance of cholesterol in each organelle are not fully understood. Here, by generating deletion mutants of ORPs in Caenorhabditis elegans, we show that ORPs are required for the formation and function of multivesicular bodies (MVBs). In an RNAi enhancer screen using obr quadruple mutants (obr-1; -2; -3; -4), we found that MVB-related genes show strong genetic interactions with the obr genes. In obr quadruple mutants, late endosomes/lysosomes are enlarged and membrane protein degradation is retarded, although endocytosed soluble proteins are normally delivered to lysosomes and degraded. We also found that the cholesterol content of late endosomes/lysosomes is reduced in the mutants. In wild-type worms, cholesterol restriction induces the formation of enlarged late endosomes/lysosomes, as observed in obr quadruple mutants, and increases embryonic lethality upon knockdown of MVB-related genes. Finally, we show that knockdown of ORP1L, a mammalian ORP family member, induces the formation of enlarged MVBs in HeLa cells. Our in vivo findings suggest that the proper cholesterol level of late endosomes/lysosomes generated by ORPs is required for normal MVB formation and MVB-mediated membrane protein degradation.
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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.