國家衛生研究院 NHRI:Item 3990099045/13871
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    題名: Dihydroceramide desaturase promotes the formation of intraluminal vesicles and inhibits autophagy to increase exosome production
    作者: Wu, CY;Jhang, JG;Lin, WS;Chuang, PH;Lin, CW;Chu, LA;Chiang, AS;Ho, HC;Chan, CC;Huang, SY
    貢獻者: Institute of Molecular and Genomic Medicine
    摘要: Exosomes are important for cell–cell communication. Deficiencies in the human dihydroceramide desaturase gene, DEGS1, increase the dihydroceramide-to-ceramide ratio and cause hypomyelinating leukodystrophy. However, the disease mechanism remains unknown. Here, we developed an in vivo assay with spatially controlled expression of exosome markers in Drosophila eye imaginal discs and showed that the level and activity of the DEGS1 ortholog, Ifc, correlated with exosome production. Knocking out ifc decreased the density of the exosome precursor intraluminal vesicles (ILVs) in the multivesicular endosomes (MVEs) and reduced the number of exosomes released. While ifc overexpression and autophagy inhibition both enhanced exosome production, combining the two had no additive effect. Moreover, DEGS1 activity was sufficient to drive ILV formation in vitro. Together, DEGS1/Ifc controls the dihydroceramide-to-ceramide ratio and enhances exosome secretion by promoting ILV formation and preventing the autophagic degradation of MVEs. These findings provide a potential cause for the neuropathy associated with DEGS1-deficient mutations.
    日期: 2021-12-17
    關聯: iScience. 2021 Dec 17;24(12):Article number 103437.
    Link to: http://dx.doi.org/10.1016/j.isci.2021.103437
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2589-0042&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000740254600005
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85119971342
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