Maternal Phosphatase Inhibitor-2 Is Required for Proper Chromosome Segregation and Mitotic Synchrony During Drosophila Embryogenesis

Abstract

Protein phosphatase-1 (PP1) is a major Ser/Thr phosphatase conserved among all eukaryotes, present as the essential GLC7 gene in yeast. Inhibitor-2 (I-2) is an ancient PP1 regulator, named GLC8 in yeast, but its in vivo function is unknown. Unlike mammals with multiple I-2 genes, in Drosophila there is a single I-2 gene, and here we describe its maternally derived expression and required function during embryogenesis. During oogenesis, germline expression of I-2 results in the accumulation of RNA and abundant protein in unfertilized eggs; in embryos, the endogenous I-2 protein concentrates around condensed chromosomes during mitosis and also surrounds interphase nuclei. An I-2 loss-of-function genotype is associated with a maternal-effect phenotype that results in drastically reduced progeny viability, as measured by reduced embryonic hatch rates and larval lethality. Embryos derived from I-2 mutant mothers show faulty chromosome segregation and loss of mitotic synchrony in cleavage-stage embryos, patchy loss of nuclei in syncytial blastoderms, and cuticular pattern defects in late-stage embryos. Transgenic expression of wild-type I-2 in mutant mothers gives dose-dependent rescue of the maternal effect on embryo hatch rate. We propose that I-2 is required for proper chromosome segregation during Drosophila embryogenesis through the coordinated regulation of PP1 and Aurora B.

Protein Kinase CK2 Regulates the Dimerization of Histone Deacetylase 1 (HDAC1) and HDAC2 during Mitosis

“…Further, protein phosphatase 2A is excluded from the nucleus in early prophase, whereas CK2 remains nuclear until prometaphase (25). Also, protein phosphatase 1 activity is low until metaphase and increases at the metaphase-anaphase transition period (26). Our studies show that the highly phosphorylated state of HDAC2 is due to the activity of CK2.…”

Phosphatase Inhibitor-2 Balances Protein Phosphatase 1 and Aurora B Kinase for Chromosome Segregation and Cytokinesis in Human Retinal Epithelial Cells

“…In Drosophila, I-2 is a maternal function gene and the I-2 protein is loaded into the oocyte for early rounds of mitosis within the syncytial embryo (Wang et al, 2008). Embryos of mutant mothers with reduced levels of I-2 exhibit defects in chromosome segregation, with DNA bridges linking adjacent nuclei, and they show loss of synchrony of mitosis across the embryo (Wang et al, 2008). Reduction of maternal I-2 levels results in a profound loss of viability in terms of hatching rate and survival of the larvae, effects that are partially rescued by dose-dependent transgenic expression of Drosophila I-2.…”

Plasmodium falciparumencodes a conserved active inhibitor-2 for Protein Phosphatase type 1: perspectives for novel anti-plasmodial therapy

“…Moreover, exploration of the role of I2 in Drosophila development evidenced that an I2 loss-of-function in mothers leads to a dramatic reduction in the viability of progeny as measured by a decrease in embryonic hatch rates and larval lethality. However, I2 gain-of-function by transgenic expression of I2 in mutant mothers reversed this effect [40]. Altogether, these observations indicate that I2 plays a critical role in achieving successful mitosis and it is apparent that interfering with I2 functions represents an attractive approach for pharmacological intervention.…”