Identification of a novel multiprotein complex in cargo sorting that preserves metabolic pathways in the liver

Alina Fedoseienko

    Onderzoeksoutput: Thesis fully internal (DIV)

    1305 Downloads (Pure)


    Scaffold proteins are crucial regulators of a diverse array of biological processes. This thesis aims to better understand the function of the relatively new family of scaffold proteins called the COMMD proteins. COMMD1, the prototype of this family, has been associated with numerous diseases such as hepatic copper toxicity syndrome, hypercholesterolemia and cancer, but the biological role of the other nine members remains largely unknown.
    Our study show for the first time that in the liver COMMD6 and COMMD9 both an important role have to preserve cholesterol and copper homeostasis, similarly as we previously demonstrated for COMMD1. Interestingly, however, our data indicate that only myeloid COMMD1 prevents uncontrolled inflammation but not COMMD6 and COMMD9. We show that the COMMD proteins form together a stable multi-COMMD protein complex to regulate these cellular processes. The organization of this complex is likely cell type-specific, but the exact composition of these complexes remains unclear, and more research is wanted. Taken together our work revealed that the COMMD proteins likely act together to facilitate the endosomal trafficking of different transmembrane proteins such as LDLR and ATP7B to preserve cholesterol and copper homeostasis. We expect that better understanding of these pathways will advance therapeutic research to treat hypercholesterolemia and copper disorders.
    Originele taal-2English
    KwalificatieDoctor of Philosophy
    Toekennende instantie
    • Rijksuniversiteit Groningen
    • Hofker, Marten, Supervisor
    • van de Sluis, Bart, Supervisor
    Datum van toekenning19-sep.-2016
    Plaats van publicatie[Groningen]
    Gedrukte ISBN's978-90-367-9091-8
    Elektronische ISBN's978-90-367-9088-8
    StatusPublished - 2016

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