Because of the rapid cleavages that follow fertilization, oocytes stockpile proteins and transcribe and store mRNAs during oogenesis that will be used during oocyte maturation and early embryogenesis. The regulated translational activation of stored mRNAs ensures that their encoded proteins will arrive at the appropriate location within the developing organism, at the appropriate time. A prominent mechanism for the storage and selective translational activation of several mRNAs crucial for oocyte maturation in Xenopus and mouse requires that the mRNA contain a cytoplasmic polyadenylation element (CPE) within its 3' untranslated region (UTR) and that this sequence be bound by the CPE-binding protein (CPEB). The regulation of CPEB activity governs the transition from translational repression to translational activation for these mRNAs. Significant questions remain regarding the role of CPEB in translational repression and how CPEB activity during oocyte maturation is modulated to control differences in the timing of translational activation for different classes of mRNAs. To begin to address these questions, we sought to identify Xenopus CPEB-interacting proteins. We have identified a putative, Xenopus Rho-family guanine nucleotide exchange factor, which we have named XGef, that interacts strongly with CPEB in ovo, and advances the rate of progesterone-induced oocyte maturation. We propose that XGef positively influences oocyte maturation by activating a G-protein that facilitates the function of CPEB. In addition, we propose that the activity of XGef is mediated through its interaction with CPEB. To test our hypotheses, we will: 1) Examine the requirement for an XGef:CPEB interaction in oocyte maturation. 2) Determine if XGef exchange factor activity is required for oocyte maturation. 3) Determine when XGef functions during oocyte maturation. Further exploration of the connection between these two proteins will significantly advance our understanding of signal transduction, translational regulation, and the regulation of growth control processes, and therefore, our understanding of mechanisms central to development and cancer.
| Martinez, Susana E; Yuan, Lei; Lacza, Charlemagne et al. (2005) XGef mediates early CPEB phosphorylation during Xenopus oocyte meiotic maturation. Mol Biol Cell 16:1152-64 |
| Reverte, Carlos G; Yuan, Lei; Keady, Brian T et al. (2003) XGef is a CPEB-interacting protein involved in Xenopus oocyte maturation. Dev Biol 255:383-98 |
