Ca²⁺_cyt negatively regulates the initiation of oocyte maturation

Ca²⁺ is a ubiquitous intracellular messenger that is important for cell cycle progression. Genetic and biochemical evidence support a role for Ca²⁺ in mitosis. In contrast, there has been a long-standing debate as to whether Ca²⁺ signals are required for oocyte meiosis. Here, we show that cytoplasmic Ca²⁺ (Ca²⁺_cyt) plays a dual role during Xenopus oocyte maturation. Ca²⁺ signals are dispensable for meiosis entry (germinal vesicle breakdown and chromosome condensation), but are required for the completion of meiosis I. Interestingly, in the absence of Ca²⁺_cyt signals oocytes enter meiosis more rapidly due to faster activation of the MAPK-maturation promoting factor (MPF) kinase cascade. This Ca²⁺-dependent negative regulation of the cell cycle machinery (MAPK-MPF cascade) is due to Ca²⁺_cyt acting downstream of protein kinase A but upstream of Mos (a MAPK kinase kinase). Therefore, high Ca²⁺_cyt delays meiosis entry by negatively regulating the initiation of the MAPK-MPF cascade. These results show that Ca²⁺ modulates both the cell cycle machinery and nuclear maturation during meiosis.