Abstract
Cell division and development are regulated by networks of kinases and phosphatases. In early Drosophila embryogenesis, 13 rapid nuclear divisions take place in a syncytium, requiring fine coordination between cell cycle regulators. The Polo kinase is a conserved, crucial regulator of M-phase. We have recently reported an antagonism between Polo and Greatwall (Gwl), another mitotic kinase, in Drosophila embryos. However, the nature of the pathways linking them remained elusive. We have conducted a comprehensive screen for additional genes functioning with polo and gwl. We uncovered a strong interdependence between Polo and Protein Phosphatase 2A (PP2A) with its B-type subunit Twins (Tws). Reducing the maternal contribution of Polo and PP2A-Tws together is embryonic lethal. We found that Polo and PP2A-Tws collaborate to ensure centrosome attachment to nuclei. While a reduction in Polo activity leads to centrosome detachments observable mostly around prophase, a reduction in PP2A-Tws activity leads to centrosome detachments at mitotic exit, and a reduction in both Polo and PP2A-Tws enhances the frequency of detachments at all stages. Moreover, we show that Gwl antagonizes PP2A-Tws function in both meiosis and mitosis. Our study highlights how proper coordination of mitotic entry and exit is required during embryonic cell cycles and defines important roles for Polo and the Gwl-PP2A-Tws pathway in this process.
Highlights
The cell cycle is largely driven by networks of kinases and phosphatases that coordinate the sequential events of cell division in addition to regulating each other [1]
While in budding yeast the Cdc14 phosphatase plays a crucial role in promoting mitotic exit by dephosphorylating Cdk1 substrates and promoting its inactivation [7], it is becoming increasingly clear that a form of Protein Phosphatase 2A (PP2A) bound to a Bsubtype adaptor subunit fulfills this function in vertebrates [8,9]
We have used fly genetics to identify additional genes that function with polo and greatwall during early embryogenesis
Summary
The cell cycle is largely driven by networks of kinases and phosphatases that coordinate the sequential events of cell division in addition to regulating each other [1]. In Drosophila, the first 13 mitotic cycles occur in a syncytium at around 10–15 min intervals with virtually no zygotic transcription, and are driven by maternally contributed proteins and mRNAs [10]. In addition to organizing mitotic spindles, centrosomes are tethered to nuclei in the syncytium and constitute anchors for the nuclei to a network of anti-parallel astral microtubules (MTs) that push nuclei away from each other and towards the cortex [11]. While centrosomes are dispensable for cell division in many cell types, they are absolutely essential for early embryogenesis in Drosophila [15,16]
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