The Multiple Roles of Mps1 in Drosophila Female Meiosis

Abstract

The Drosophila gene ald encodes the fly ortholog of mps1, a conserved kinetochore-associated protein kinase required for the meiotic and mitotic spindle assembly checkpoints. Using live imaging, we demonstrate that oocytes lacking Ald/Mps1 (hereafter referred to as Ald) protein enter anaphase I immediately upon completing spindle formation, in a fashion that does not allow sufficient time for nonexchange homologs to complete their normal partitioning to opposite half spindles. This observation can explain the heightened sensitivity of nonexchange chromosomes to the meiotic effects of hypomorphic ald alleles. In one of the first studies of the female meiotic kinetochore, we show that Ald localizes to the outer edge of meiotic kinetochores after germinal vesicle breakdown, where it is often observed to be extended well away from the chromosomes. Ald also localizes to numerous filaments throughout the oocyte. These filaments, which are not observed in mitotic cells, also contain the outer kinetochore protein kinase Polo, but not the inner kinetochore proteins Incenp or Aurora-B. These filaments polymerize during early germinal vesicle breakdown, perhaps as a means of storing excess outer kinetochore kinases during early embryonic development. Female meiosis is the process that ensures developing eggs (called oocytes) receive the proper complement of chromosomes. The failure to accurately segregate chromosomes results in aneuploidy, which is the leading cause of birth defects in humans. Cells contain checkpoints that help ensure proper chromosome segregation. Here, we present a study of the Drosophila homolog of monopolar spindles 1 (mps1), which is a key checkpoint component. Mutants in mps1 produce oocytes with the wrong number of chromosomes. Using live imaging of female meiosis, we find that mps1 mutants do not delay the cell cycle as is normally observed in wild-type flies. This delay gives chromosomes the time needed to properly align before cell division, and therefore the defect caused by mps1 mutants is due to chromosomes being forced to segregate before they have had time to properly align. Additionally, we find that mps1 as well as two other checkpoint proteins localize to numerous filaments throughout the oocyte. These filaments appear to form when the nuclear envelope breaks down, and disappear late in meiosis. While the function of these structures is not known, they appear similar to filaments seen in female meiosis in nematodes, and may be required to regulate these proteins.