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APC/C‐dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10074082/ https://www.ncbi.nlm.nih.gov/pubmed/36852890 http://dx.doi.org/10.15252/embr.202255607 |
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author | Meghini, Francesco Martins, Torcato Zhang, Qian Loyer, Nicolas Trickey, Michelle Abula, Yusanjiang Yamano, Hiroyuki Januschke, Jens Kimata, Yuu |
author_facet | Meghini, Francesco Martins, Torcato Zhang, Qian Loyer, Nicolas Trickey, Michelle Abula, Yusanjiang Yamano, Hiroyuki Januschke, Jens Kimata, Yuu |
author_sort | Meghini, Francesco |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10074082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100740822023-04-06 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 Januschke, Jens Kimata, Yuu EMBO Rep Articles 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. John Wiley and Sons Inc. 2023-02-28 /pmc/articles/PMC10074082/ /pubmed/36852890 http://dx.doi.org/10.15252/embr.202255607 Text en © 2023 The Authors. Published under the terms of the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Meghini, Francesco Martins, Torcato Zhang, Qian Loyer, Nicolas Trickey, Michelle Abula, Yusanjiang Yamano, Hiroyuki Januschke, Jens Kimata, Yuu APC/C‐dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells |
title |
APC/C‐dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells |
title_full |
APC/C‐dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells |
title_fullStr |
APC/C‐dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells |
title_full_unstemmed |
APC/C‐dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells |
title_short |
APC/C‐dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells |
title_sort | apc/c‐dependent degradation of spd2 regulates centrosome asymmetry in drosophila neural stem cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10074082/ https://www.ncbi.nlm.nih.gov/pubmed/36852890 http://dx.doi.org/10.15252/embr.202255607 |
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