APC/C-Vihar regulates centrosome activity and stability in the Drosophila germline

A. L. Braun,F. Meghini, G. Villa-Fombuena, M. Guermont, E. Fernandez-Martinez,D.M. Glover, M. D. Martín-Bermudo,A. González-Reyes, Y. Kimata

biorxiv(2018)

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摘要
A universal feature of metazoan reproduction is the elimination of the maternal centrosomes prior to the end of oogenesis. In animals that have a syncytial cyst stage of oocyte development, including Drosophila and mouse, the germline centrosomes undergo a migration to all reside within the oocyte. However, the functional significance of centrosome transport within the female germline and the mechanism orchestrating this event are still a mystery. The Anaphase Promoting Complex/Cyclosome (APC/C) is a multi-subunit ubiquitin ligase (E3) that temporally regulates progression of the cell cycle as well as the centrosome cycle. By altering the negative regulation of the cooperating ubiquitin conjugating enzyme (E2), Vihar/Ube2c, we show that temporal control of APC/C activity ensures centrosome stability and migration during early Drosophila oogenesis. When there is perduring APC/C activity, Polo kinase is precociously targeted for destruction, which results in centriole instability and decreased centrosome transport to the oocyte. We show that decreased centrosome transport correlates with a decreased accumulation of pericentriolar material (PCM) proteins on the oocyte nucleus, which results in a weakening of the structural integrity of the egg chamber and loss of oocyte fate – the overall consequence being a reduction in female fertility. Considering the conserved roles of the APC/C and Polo kinase throughout the animal kingdom and the fact that many animals have a syncytial stage of egg development, our results provide insight into the general necessity of gametic centrosome transport for female fertility.
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