Journal
EMBO REPORTS
Volume 24, Issue 4, Pages -Publisher
WILEY
DOI: 10.15252/embr.202255607
Keywords
asymmetric cell division; cell cycle; centrosome; stem cell; ubiquitination
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A functional centrosome is crucial for animal development and physiology. In addition to regulating centriole duplication, ubiquitin-mediated proteolysis plays a vital role in controlling the precise regulation of centrosome. The research conducted on Drosophila demonstrates that APC/C-Fzr controls the levels of Spd2 to affect neural stem cell-specific asymmetric PCM recruitment and microtubule nucleation at interphase centrosomes. Furthermore, APC/C-Fzr-dependent Spd2 degradation facilitates the accumulation of Polo-dependent Spd2 phosphorylation for PCM recruitment.
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.
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