APC/C-dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells

Francesco Meghini, Torcato Martins, Qian Zhang, Nicolas Loyer, Michelle Trickey, Yusanjiang Abula, Hiroyuki Yamano, Jens Januschke (Lead / Corresponding author), Yuu Kimata (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)
    39 Downloads (Pure)

    Abstract

    A functional centrosome is vital for the development and physiology of animals. Among numerous regulatory mechanisms of the centrosome, ubiquitin-mediated proteolysis is known to be critical for the precise regulation of centriole duplication. However, its significance beyond centrosome copy number control remains unclear. Using an in vitro screen for centrosomal substrates of the APC/C ubiquitin ligase in Drosophila, we identify several conserved pericentriolar material (PCM) components, including the inner PCM protein Spd2. We show that Spd2 levels are controlled by the interphase-specific form of APC/C, APC/C Fzr, in cultured cells and developing brains. Increased Spd2 levels compromise neural stem cell–specific asymmetric PCM recruitment and microtubule nucleation at interphase centrosomes, resulting in partial randomisation of the division axis and segregation patterns of the daughter centrosome in the following mitosis. We further provide evidence that APC/C Fzr-dependent Spd2 degradation restricts the amount and mobility of Spd2 at the daughter centrosome, thereby facilitating the accumulation of Polo-dependent Spd2 phosphorylation for PCM recruitment. Our study underpins the critical role of cell cycle–dependent proteolytic regulation of the PCM in stem cells.

    Original languageEnglish
    Article numbere55607
    Number of pages18
    JournalEMBO Reports
    Volume24
    Issue number4
    Early online date28 Feb 2023
    DOIs
    Publication statusPublished - 5 Apr 2023

    Keywords

    • asymmetric cell division
    • cell cycle
    • centrosome
    • stem cell
    • ubiquitination

    ASJC Scopus subject areas

    • Genetics
    • Molecular Biology
    • Biochemistry

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