The oocyte-to-embryo transition requires APC/C mediated destruction of Matrimony, a POLO kinase inhibitor. Zachary J. Whitfield¹, Jennifer Chisholm², R. Scott Hawley², Terry L. Orr-Weaver¹. 1) Whitehead Institute for Biomedical Research, MIT, Cambridge, MA; 2) Stowers Institute for Medical Research, Kansas City, MO.

   The oocyte-to-embryo transition requires a cell cycle change from meiosis to mitosis. A female meiosis-specific form of the Anaphase Promoting Complex/Cyclosome, activated by the Cortex Cdc20 protein (APC^Cort), is essential for the completion of meiosis in the Drosophila egg. The APC/C ubiquitylates substrates to target them for degradation, and its activity is critical for anaphase onset. We investigated whether APC^Cort could target one or more meiotic proteins whose degradation would be necessary for mitosis to proceed properly.
   To identify substrates of APC^Cort, we used IP/mass spectrometry to define binding partners of Cortex and quantitative mass spectrometry to identify proteins whose levels were elevated in cortex mutant eggs. Both approaches identified Matrimony, an inhibitor of POLO kinase during prophase of meiosis I in the oocyte. Several observations confirm Matrimony is a critical APC^Cort target. We found Matrimony protein levels drop drastically after completion of meiosis, and confirmed that Matrimonys protein levels are elevated in cortex mutant eggs by western blotting. Furthermore, Matrimony levels also are increased in eggs mutant for morula/apc2, a component of the APC/C, but not in fzy/cdc20 mutant eggs, another APC/C activator. Additionally, when introduced into Kc cells, functional Cortex leads to reduced levels of Matrimony protein, consistent with Matrimony being a specific substrate of APC^Cort. We have identified motifs in Matrimony required for its degradation. Overexpression of Matrimony using the UAS/GAL4 system caused a subset of embryos to exhibit mitotic defects and developmental arrest, and these are dominantly enhanced by polo mutations. Thus down regulation of Matrimony at the oocyte-to-embryo transition by APC^Cort activity is important for adequate levels of POLO activity to ensure proper embryogenesis.