title: Myt1 inhibition of Cyclin A/Cdk1 is essential for fusome integrity and premeiotic centriole engagement in Drosophila spermatocytes.
abstract: Regulation of cell cycle arrest in premeiotic G2 phase coordinates germ cell maturation and meiotic cell division with hormonal and developmental signals by mechanisms that control Cyclin B synthesis and inhibitory phosphorylation of the M-phase kinase, Cdk1. In this study, we investigated how inhibitory phosphorylation of Cdk1 by Myt1 kinase regulates premeiotic G2 phase of Drosophila male meiosis. Immature spermatocytes lacking Myt1 activity exhibit two distinct defects: disrupted intercellular bridges (fusomes) and premature centriole disengagement. As a result, the myt1 mutant spermatocytes enter meiosis with multipolar spindles. These myt1 defects can be suppressed by depletion of Cyclin A activity or ectopic expression of Wee1 (a partially redundant Cdk1 inhibitory kinase) and phenocopied by expression of a Cdk1F mutant defective for inhibitory phosphorylation. We therefore conclude that Myt1 inhibition of Cyclin A/Cdk1 is essential for normal fusome behavior and centriole engagement during premeiotic G2 arrest of Drosophila male meiosis. The novel meiotic functions we discovered for Myt1 kinase are spatially and temporally distinct from previously described functions of Myt1 as an inhibitor of Cyclin B/Cdk1 to regulate G2/MI timing.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.
authors.forename: Ramya
authors.initials: R
authors.lastname: Varadarajan
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ayeni
authors.affiliation: Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 2E9, Canada.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.
authors.forename: Ellen
authors.initials: E
authors.lastname: Homola
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada shelagh.campbell@ualberta.ca.
authors.forename: Shelagh D
authors.initials: SD
authors.lastname: Campbell
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002502:Centrioles / Q000378:metabolism; D019925:Cyclin A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D016195:G2 Phase; D008297:Male; D008540:Meiosis; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D019925:Cyclin A; D019926:Cyclin B; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D011494:Protein Kinases; C458479:Myt1 protein, Drosophila; D016203:CDC2 Protein Kinase; C000601753:Cdk1 protein, Drosophila