Sorting out cholesterol metabolism: novel insights into the mechanism of endosomal trafficking of lipoprotein receptors

Melinde Wijers

    Research output: ThesisThesis fully internal (DIV)

    846 Downloads (Pure)

    Abstract

    This thesis highlights a crucial role for the CCC and WASH complexes in hepatic cholesterol uptake by orchestrating the endosomal recycling of LDLR, LRP1 and SR-BI. We provided novel insights into how the different CCC components interrelate to maintain the integrity of the CCC complex. We introduced somatic CRISPR/Cas9 gene editing technology, a sophisticated methodology to study the interplay between different endosomal sorting complexes in vivo. Using this technology, we found that both retriever and retromer likely participate in the CCC-WASH axis to facilitate endosomal recycling of LDLR, but not SR-BI. Moreover, we showed that hepatic retromer controls plasma TG levels independently of the CCC-WASH pathway. Overall, this thesis provides novel insights into the intricate interplay between the different protein complexes of endosomal sorting machineries in the regulation of lipid metabolism.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • van de Sluis, Bart, Supervisor
    • Kuivenhoven, Jan Albert, Supervisor
    Award date20-Nov-2019
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-034-2110-0
    Electronic ISBNs978-94-034-2109-4
    DOIs
    Publication statusPublished - 2019

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