The C . elegans Myt 1 ortholog is required for the proper timing of oocyte maturation Anna

Abstract

INTRODUCTION Oocyte growth and differentiation (oogenesis) are crucial for fertilization competency and the rapid cell divisions of early embryonic development. The developing oocyte is essentially a synthetic factory and maternal storehouse for the factors required for these processes. Maternal factors that trigger cell proliferation must be strictly inhibited so that the oocyte remains in meiotic prophase and does not advance in the cell cycle precociously. How these factors are inhibited is poorly understood. In most animals, oocytes arrest in prophase of meiosis I once oocyte growth is complete. In contrast to mitotic prophase, meiotic prophase in immature oocytes can be a long-lived stage that is marked by extensive transcriptional and translational activity, analogous to a G2-like phase. The growth phase of oogenesis is followed by oocyte maturation, whereby an external signal instructs the oocyte to mature. The source and form of this signal varies throughout the animal kingdom (Voronina and Wessel, 2003). The hallmarks of oocyte maturation in many organisms are nuclear envelope breakdown (NEBD), chromosome congression, and the resumption of meiosis. The meiotic divisions generate the fertilization-competent haploid oocyte and the polar bodies. The timing of fertilization relative to the completion of the meiotic divisions varies among species (Voronina and Wessel, 2003). In C. elegans, fertilization triggers the completion of the meiotic divisions and the initiation of zygotic development. MPF is universally required for oocyte maturation and the transition from G2 to M during the mitotic divisions (Schmitt and Nebreda, 2002). MPF is a complex of a cyclin-dependent kinase, Cdk1, and its partner, cyclin B (Doree and Hunt, 2002). This complex phosphorylates key substrates to promote chromosome condensation, NEBD, and spindle assembly in meiotic and mitotic cells. MPF is synthesized during oogenesis but must be kept inactive until it is required for oocyte maturation and the subsequent embryonic mitoses. The activity of Cdk1/cyclin B is modulated by phosphorylation, dephosphorylation and cyclin degradation (Coleman and Dunphy, 1994). Although the complex exists in interphase, it is inactive. Cdk1 is phosphorylated by the Cdk-activating kinase CAK, on Thr161 (for human Cdk1), and by an inhibitory kinase, Wee1/Myt1, on Thr14 (T14) and Tyr15 (Y15). This triply phosphorylated Cdk1 is activated at the G2/M transition by the dephosphorylation of T14 and Y15 by the dual-specificity phosphatase Cdc25. Likewise, the kinases and phosphatases that regulate Cdk1 are also subject to positive and negative regulation. Cyclin B degradation during mitotic exit ensures that the complex is inactivated for the next cell cycle. It is thus the fine balance of these positive and negative regulators that controls Cdk1 activity during meiosis and mitosis. Although the biochemistry of MPF and its regulation have been extensively studied (Schmitt and Nebreda, 2002), much less is understood about the mechanism(s) used to maintain a G2like state within the immature oocyte. This developmental program might rely upon a Wee1 family member to ensure that MPF is kept inactive. Myt1 is a membrane-associated member of the Wee1 family and antibody depletion in Xenopus oocytes leads to precocious NEBD, presumably through the activation of Cdk1 (Nakajo et al., 2000). Evidence suggests that Myt1 is inhibited and Cdc25 is stimulated to promote the activation and onset of oocyte maturation in Xenopus oocytes (Schmitt and Nebreda, 2002). Abnormalities in the coordination between the cell cycle regulators and the developmental program of oocytes are likely to have devastating consequences. The C. elegans Myt1 ortholog is required for the proper timing of oocyte maturation

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@inproceedings{Burrows2006TheC, title={The C . elegans Myt 1 ortholog is required for the proper timing of oocyte maturation Anna}, author={Erik Burrows and Bonnielin K . Sceurman and Mary E . Kosinski and Christopher T . Richie and Penny L . Sadler and J. M. Schumacher and Andy Golden}, year={2006} }