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

Authors: Meghini, Francesco; Martins, Torcato; Zhang, Qian; Loyer, Nicolas; Trickey, Michelle; Abula, Yusanjiang; Yamano, Hiroyuki; +2 Authors

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

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.

Funder: Marie Curie (Marie Curie Cancer Care); Id: http://dx.doi.org/10.13039/501100000654

Country
United Kingdom
Keywords

Centrosome, Mitosis, ubiquitination, Biochemistry, asymmetric cell division, stem cell, Neural Stem Cells, Genetics, Animals, cell cycle, Drosophila, Ubiquitins, Molecular Biology, 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, Centrioles

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
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