Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pgen.1001055
Title: Multivesicular body formation requires OSBP-related proteins and cholesterol
Authors: Kobuna H.
Inoue T. 
Shibata M.
Gengyo-Ando K.
Yamamoto A.
Mitani S.
Arai H.
Keywords: carrier protein
cholesterol
oxysterol binding protein related protein
unclassified drug
article
Caenorhabditis elegans
cell enlargement
cell organelle
controlled study
embryo death
endocytosis
endosome
gene interaction
HeLa cell
human
human cell
lysosome
mulltivesicular body
mutant
nonhuman
nucleotide sequence
protein degradation
protein function
protein transport
RNA interference
wild type
Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Cholesterol
Hela Cells
Humans
Multigene Family
Multivesicular Bodies
Receptors, Steroid
Caenorhabditis elegans
Eukaryota
Mammalia
Issue Date: 2010
Citation: Kobuna H., Inoue T., Shibata M., Gengyo-Ando K., Yamamoto A., Mitani S., Arai H. (2010). Multivesicular body formation requires OSBP-related proteins and cholesterol. PLoS Genetics 6 (8). ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pgen.1001055
Rights: Attribution 4.0 International
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. © 2010 Kobuna et al.
Source Title: PLoS Genetics
URI: https://scholarbank.nus.edu.sg/handle/10635/161659
ISSN: 15537390
DOI: 10.1371/journal.pgen.1001055
Rights: Attribution 4.0 International
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