The careful control of Polo kinase by APC/C-Ube2C ensures the intercellular transport of germline centrosomes during Drosophila oogenesis.

Alexis Leah Braun,Acaimo González-Reyes,David Moore Glover,Francesco Meghini,Maria Dolores Martín-Bermudo,Zhang Qian,Elisa Fernandez-Martinez,Yuu Kimata,Gema Villa-Fombuena,Morgane Guermont

doi:10.1098/rsob.200371

Abstract

A feature of metazoan reproduction is the elimination of maternal centrosomes from the oocyte. In animals that form syncytial cysts during oogenesis, including Drosophila and human, all centrosomes within the cyst migrate to the oocyte where they are subsequently degenerated. The importance and the underlying mechanism of this event remain unclear. Here, we show that, during early Drosophila oogenesis, control of the Anaphase Promoting Complex/Cyclosome (APC/C), the ubiquitin ligase complex essential for cell cycle control, ensures proper transport of centrosomes into the oocyte through the regulation of Polo/Plk1 kinase, a critical regulator of the integrity and activity of the centrosome. We show that novel mutations in the APC/C-specific E2, Vihar/Ube2c, that affect its inhibitory regulation on APC/C cause precocious Polo degradation and impedes centrosome transport, through destabilization of centrosomes. The failure of centrosome migration correlates with weakened microtubule polarization in the cyst and allows ectopic microtubule nucleation in nurse cells, leading to the loss of oocyte identity. These results suggest a role for centrosome migration in oocyte fate maintenance through the concentration and confinement of microtubule nucleation activity into the oocyte. Considering the conserved roles of APC/C and Polo throughout the animal kingdom, our findings may be translated into other animals.

Highlights

The centrosome is a major microtubule-organizing centre (MTOC) in many animal cells and, through microtubule nucleation, regulates a wide range of cellular processes during development and in adult tissues [1,2]
We show that vihΔN mutations probably cause the upregulation of Anaphase Promoting Complex/Cyclosome (APC/C), which in turn leads to the reduction of Polo kinase, one of the APC/C substrates and the critical regulator of the integrity and microtubule nucleation activity of the centrosome, in developing egg chambers
The intracellular transport of germline centrosomes following cyst formation is observed in diverse animals from insects to mammals, suggesting its functional significance in oogenesis

Summary

Introduction

The centrosome is a major microtubule-organizing centre (MTOC) in many animal cells and, through microtubule nucleation, regulates a wide range of cellular processes during development and in adult tissues [1,2]. The cystoblast undergoes exactly four rounds of mitotic divisions with incomplete cytokinesis to create a 16cell syncytial cyst, in which only one cell eventually becomes the oocyte, whereas the other cells take on a nurse cell fate During this process, germline centrosomes of the cystocytes exhibit a very peculiar behaviour: virtually, all the 32 centrosomes intercellularly migrate within the cyst to eventually accumulate in one cell, the future oocyte [7]. Germline centrosomes of the cystocytes exhibit a very peculiar behaviour: virtually, all the 32 centrosomes intercellularly migrate within the cyst to eventually accumulate in one cell, the future oocyte [7] This migration coincides with the events that mark the specification of the oocyte: the concentration of fate determinants such as Bicaudal-D (BicD), Egalitarian (Egl) and Oo18 RNA-binding protein (Orb) [10,11,12,13], and the restriction of synaptonemal complexes to the oocyte [14]. Despite the universality of this phenomenon, its significance, as well as the molecular mechanism directing this process, remains elusive

Methods

Results

Conclusion