In most animals, female meiosis completes only after fertilization. Sperm entry has been implicated in providing a signal for the initiation of the final meiotic processes, however, a maternal component required for this has not been previously identified. We report the characterization of a novel family of three highly similar paralogs (memi-1, memi-2, memi-3) that encode oocyte-specific proteins. A temperature-sensitive dominant mutation, memi-1(sb41), was originally identified in a screen for maternal-effect lethal mutations in the Mains laboratory (formerly termed mel-43)1. memi-1(sb41) behaves as a hypermorphic mutation, and embryos from mutant mothers fail to exit female meiosis II properly. A memi-1(deletion) exhibits no obvious phenotype, however, loss of all three memi paralogs via RNAi causes fertilized oocytes to abort meiosis I during anaphase, “skip” meiosis II, and proceed directly into mitosis. The McNally lab showed that a similar phenotype occurs when sperm-activated oocytes are not fertilized2, suggesting that the MEMI proteins represent a maternal component of a post-fertilization signal that specifies the meiosis II program. The MEMI proteins are degraded before mitosis and sensitive to ZYG-11, a substrate-specific adapter for cullin-based ubiquitin ligase activity3,4. Interestingly, the memi-1(sb41) hypermorphic mutation results in inappropriate persistence of MEMI-1, but not MEMI-2 or MEMI-3, protein into mitosis. In order to identify potential activators of the memi pathway, we performed an RNAi screen for suppressors of memi-1(sb41). This approach identified a sperm-specific PP1 phosphatase. Because reducing the funciton of this PP1 phosphatase suppresses memi-1(sb41), the PP1 might also be required for normal memi activity upon fertilization. We are currently testing the hypothesis that sperm-delivered PP1 activates MEMI to specify meiosis II after fertilization.
1Mitenko, N. L., Eisner, J. R., Swiston, J. R. and Mains, P. E. (1997) Genetics 147(4): 1665-74. 2McNally, K. L. and McNally, F. J. (2005) Dev Biol 282(1): 218-30. 3Sonneville, R. and Gonczy, P. (2004) Development 131(15): 3527-43. 4Vasudevan, S., Starostina, N. G. and Kipreos, E. T. (2007) EMBO Rep 8(3): 279-86.