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

Melinde Wijers

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    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.
    Originele taal-2English
    KwalificatieDoctor of Philosophy
    Toekennende instantie
    • Rijksuniversiteit Groningen
    Begeleider(s)/adviseur
    • van de Sluis, Bart, Supervisor
    • Kuivenhoven, Jan Albert, Supervisor
    Datum van toekenning20-nov-2019
    Plaats van publicatie[Groningen]
    Uitgever
    Gedrukte ISBN's978-94-034-2110-0
    Elektronische ISBN's978-94-034-2109-4
    DOI's
    StatusPublished - 2019

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