APC/C-dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells
2023
发表期刊EMBO REPORTS; (IF:6.5[JCR-2023],8.3[5-Year])
ISSN1469-221X
EISSN1469-3178
DOI10.15252/embr.202255607
摘要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.
关键词asymmetric cell division cell cycle centrosome stem cell ubiquitination
学科门类Biochemistry ; Molecular Biology ; Genetics
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收录类别SCOPUS
语种英语
原始文献类型Article
Scopus 记录号2-s2.0-85149273769
来源库SCOPUS
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/286497
专题生命科学与技术学院
生命科学与技术学院_博士生
生命科学与技术学院_PI研究组_Yuu Kimita组
作者单位
1.Department of Genetics,University of Cambridge,Cambridge,United Kingdom;
2.Department of Medical Sciences,Institute of Biomedicine-iBiMED,University of Aveiro,Aveiro,Portugal;
3.School of Life Science and Technology,ShanghaiTech University,Shanghai,China;
4.School of Life Science,University of Dundee,Dundee,United Kingdom;
5.UCL Cancer Institute,University College London,London,United Kingdom
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GB/T 7714
Meghini, Francesco,Martins, Torcato,Zhang, Qian,et al. APC/C-dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells[J]. EMBO REPORTS;,2023.
APA Meghini, Francesco.,Martins, Torcato.,Zhang, Qian.,Loyer, Nicolas.,Trickey, Michelle.,...&Kimata, Yuu.(2023).APC/C-dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells.EMBO REPORTS;.
MLA Meghini, Francesco,et al."APC/C-dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells".EMBO REPORTS; (2023).
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