Abstract
Polo is a conserved kinase that coordinates many events of mitosis and meiosis, but how it is regulated remains unclear. Drosophila females having only one wild-type allele of the polo kinase gene and the dominant Scant mutation produce embryos in which one of the centrosomes detaches from the nuclear envelope in late prophase. We show that Scant creates a hyperactive form of Greatwall (Gwl) with altered specificity in vitro, another protein kinase recently implicated in mitotic entry in Drosophila and Xenopus. Excess Gwl activity in embryos causes developmental failure that can be rescued by increasing maternal Polo dosage, indicating that coordination between the two mitotic kinases is crucial for mitotic progression. Revertant alleles of Scant that restore fertility to polo–Scant heterozygous females are recessive alleles or deficiencies of gwl; they show chromatin condensation defects and anaphase bridges in larval neuroblasts. One recessive mutant allele specifically disrupts a Gwl isoform strongly expressed during vitellogenesis. Females hemizygous for this allele are sterile, and their oocytes fail to arrest in metaphase I of meiosis; both homologues and sister chromatids separate on elongated meiotic spindles with little or no segregation. This allelic series of gwl mutants highlights the multiple roles of Gwl in both mitotic and meiotic progression. Our results indicate that Gwl activity antagonizes Polo and thus identify an important regulatory interaction of the cell cycle.
Highlights
Reversible protein phosphorylation and periodic protein destruction play major roles in regulating the eukaryotic cell division cycle
Coordination of cell division in development requires a complex interplay between protein kinases, which catalyze the transfer of phosphates to specific substrate proteins to modify their activities
Too much Greatwall activity relative to Polo leads to developmental defects in early syncytial embryos, which are initiated by the detachment of a single centrosome from the nuclear envelope in prophase
Summary
Reversible protein phosphorylation and periodic protein destruction play major roles in regulating the eukaryotic cell division cycle. Polo was initially found to be essential for centrosome maturation and separation [2] It promotes recruitment of the c-tubulin ring complex and phosphorylates Asp to facilitate nucleation of an increased number of dynamic microtubules on mitotic entry (reviewed by [4]). At the G2/M transition, Polo (Polo-like kinase 1 in vertebrates) phosphorylates and activates the Cdc phosphatase responsible for removing inhibitory phosphates on Cdk; this promotes mitotic entry [5]. It functions at the kinetochore-microtubule interface to monitor tension; the 3F3/2 phospho-epitope seen on kinetochores in the absence of tension is a consequence of Plk1/Plx kinase activity in vertebrates [6,7]. The growing list of Polo kinase substrates is evidence of its role in multiple mitotic events
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