DNAJB6 and its substrates: connecting the dots

Els Kuiper

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    Our life expectancy has increased over the last decades, but higher age is associated with more diseases. A frequent cause of age-related diseases is the formation of protein aggregates that are thought to drive several muscular and neurodegenerative diseases. With our research we want to increase the knowledge on how our cells cope with protein aggregation. Important for this is the quality control of aggregation-prone proteins, mainly provided by chaperones, and we focus on one of them: DNAJB6.

    DNAJB6 can recognize and prevent a specific form of protein aggregation: amyloid aggregation. Amyloids have a densely packed structure and are observed in diseases like Alzheimer’s and Huntington’s. The appearance of amyloids is not limited to harmful disease-related aggregates, but can also be formed by functional proteins with disordered regions that perform important tasks in our cells. Due to their disordered regions, these frequently end up in harmful aggregates. Therefore, their quality control is crucial. There is still little known about this process and if chaperones are involved.

    Proteins of the nuclear pore complex (NPC), which ensure transport between the nucleus and the rest of the cell, are a good example of these disordered proteins. Wear of NPCs and nucleocytoplasmic transport defects are associated with ageing and age-related diseases. We find that DNAJB6 can prevent NPC protein aggregation. This suggests for the first time a link between DNAJB6 and normal proteins that can form amyloids. It shows the importance of DNAJB6 for protection of such proteins under physiological circumstances and in disease.
    Originele taal-2English
    KwalificatieDoctor of Philosophy
    Toekennende instantie
    • Rijksuniversiteit Groningen
    Begeleider(s)/adviseur
    • Kampinga, Harrie, Supervisor
    • Bergink, Steven, Co-supervisor
    Datum van toekenning28-feb-2022
    Plaats van publicatie[Groningen]
    Uitgever
    DOI's
    StatusPublished - 2022

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