Mutations in Drosophila Greatwall/Scant reveal its roles in mitosis and meiosis and interdependence with Polo kinase
- PMID: 17997611
- PMCID: PMC2065886
- DOI: 10.1371/journal.pgen.0030200
Mutations in Drosophila Greatwall/Scant reveal its roles in mitosis and meiosis and interdependence with Polo kinase
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.
Conflict of interest statement
Competing interests. The authors have declared that no competing interests exist.
Figures









Similar articles
-
Suppression of scant identifies Endos as a substrate of greatwall kinase and a negative regulator of protein phosphatase 2A in mitosis.PLoS Genet. 2011 Aug;7(8):e1002225. doi: 10.1371/journal.pgen.1002225. Epub 2011 Aug 11. PLoS Genet. 2011. PMID: 21852956 Free PMC article.
-
PP2A-twins is antagonized by greatwall and collaborates with polo for cell cycle progression and centrosome attachment to nuclei in drosophila embryos.PLoS Genet. 2011 Aug;7(8):e1002227. doi: 10.1371/journal.pgen.1002227. Epub 2011 Aug 11. PLoS Genet. 2011. PMID: 21852958 Free PMC article.
-
Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression.J Cell Biol. 2013 Jul 22;202(2):277-93. doi: 10.1083/jcb.201211141. Epub 2013 Jul 15. J Cell Biol. 2013. PMID: 23857770 Free PMC article.
-
Polo kinase and progression through M phase in Drosophila: a perspective from the spindle poles.Oncogene. 2005 Jan 10;24(2):230-7. doi: 10.1038/sj.onc.1208279. Oncogene. 2005. PMID: 15640838 Review.
-
Dynamic changes in nuclear architecture during mitosis: on the role of protein phosphorylation in spindle assembly and chromosome segregation.Exp Cell Res. 1996 Dec 15;229(2):174-80. doi: 10.1006/excr.1996.0356. Exp Cell Res. 1996. PMID: 8986594 Review.
Cited by
-
Protein Phosphatases Involved in Regulating Mitosis: Facts and Hypotheses.Mol Cells. 2016 Sep;39(9):654-62. doi: 10.14348/molcells.2016.0214. Epub 2016 Sep 27. Mol Cells. 2016. PMID: 27669825 Free PMC article. Review.
-
Evidence for a role of spindle matrix formation in cell cycle progression by antibody perturbation.PLoS One. 2018 Nov 28;13(11):e0208022. doi: 10.1371/journal.pone.0208022. eCollection 2018. PLoS One. 2018. PMID: 30485354 Free PMC article.
-
The ATM-E6AP-MASTL axis mediates DNA damage checkpoint recovery.Elife. 2023 Sep 6;12:RP86976. doi: 10.7554/eLife.86976. Elife. 2023. PMID: 37672026 Free PMC article.
-
Cyclin B-Cdk1 inhibits protein phosphatase PP2A-B55 via a Greatwall kinase-independent mechanism.J Cell Biol. 2014 Mar 17;204(6):881-9. doi: 10.1083/jcb.201307160. Epub 2014 Mar 10. J Cell Biol. 2014. PMID: 24616226 Free PMC article.
-
Polo, greatwall, and protein phosphatase PP2A Jostle for pole position.PLoS Genet. 2011 Aug;7(8):e1002213. doi: 10.1371/journal.pgen.1002213. Epub 2011 Aug 11. PLoS Genet. 2011. PMID: 21852954 Free PMC article. No abstract available.
References
-
- Morgan DO. Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu Rev Cell Dev Biol. 1997;13:261–291. - PubMed
-
- Sunkel CE, Glover DM. polo, a mitotic mutant of Drosophila displaying abnormal spindle poles. J Cell Sci. 1988;89:25–38. - PubMed
-
- Llamazares S, Moreira A, Tavares A, Girdham C, Spruce BA, et al. polo encodes a protein kinase homolog required for mitosis in Drosophila. Genes Dev. 1991;5:2153–2165. - PubMed
-
- Glover DM. Polo kinase and progression through M phase in Drosophila: a perspective from the spindle poles. Oncogene. 2005;24:230–237. - PubMed
-
- Kumagai A, Dunphy WG. Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts. Science. 1996;273:1377–1380. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases