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

Meghini, Francesco; Martins, Torcato; Zhang, Qian; Loyer, Nicolas; Trickey, Michelle; Abula, Yusanjiang; Yamano, Hiroyuki; ... Kimata, Yuu; + view all (2023) APC/C-dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells. EMBO Reports , Article e55607. 10.15252/embr.202255607. Green open access

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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/CFzr, 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/CFzr-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.

Type: Article
Title: APC/C-dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embr.202255607
Publisher version: https://doi.org/10.15252/embr.202255607
Language: English
Additional information: License: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, asymmetric cell division, cell cycle, centrosome, stem cell, ubiquitination, PERICENTRIOLAR MATERIAL, MITOTIC SPINDLE, AURORA-A, CENTRIOLE DUPLICATION, S2 CELLS, KINASE 1, PROTEIN, CYCLE, POLO, COMPLEX
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10167190
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