Translational unmasking of Emi2 directs cytostatic factor arrest in meiosis II

University of Massachusetts Amherst, Amherst Center, Massachusetts, United States
Cell cycle (Georgetown, Tex.) (Impact Factor: 5.24). 04/2007; 6(6):725-31. DOI: 10.4161/cc.6.6.3936
Source: PubMed

ABSTRACT Cytostatic factor (CSF) arrests unfertilized vertebrate eggs in metaphase of meiosis II by inhibiting the anaphase-promoting complex/cyclosome (APC/C) from mediating cyclin destruction. The APC/C inhibitor Emi2/XErp1 satisfies a number of historical criteria for the molecular identification of CSF, but the mechanism by which CSF is activated selectively in meiosis II is the remaining unexplained criterion. Here we provide an explanation by showing that Emi2 is expressed specifically in meiosis II through translational de-repression or "unmasking" of its mRNA. We find that Emi2 protein is undetectable in immature, G2/prophase-arrested Xenopus oocytes and accumulates approximately 90 minutes after germinal vesicle breakdown. The 3' untranslated region of Emi2 mRNA contains cytoplasmic polyadenylation elements that directly bind the CPEB protein and confer temporal regulation of Emi2 polyadenylation and translation. Our results demonstrate that cytoplasmic polyadenylation and translational unmasking of Emi2 directs meiosis II-specific CSF arrest.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Özet Fertilizasyon, yumurta ve sperm arasında gerçekleşen, birbirini takip eden bir takım kompleks etkileşimleri içeren oldukça karmaşık bir süreçtir. Bu olaylar folikülden olgunlaşmış yumurtanın atımı ile başlar, yumurtaya sperm girişinden sonra 2 pronukleusun oluşması ve 1. mitoz bölünmenin gerçekleşmesiyle sona erer. İnsanlarda ve bütün hayvanlarda türün devamlılığı için gerekli olan bu süreç her zaman bilim adamlarının dikkatini çekmiştir. Biz de çalışmamızda fertilizasyon olayının tüm aşamalarında hangi sinyalizasyon ağlarının rol aldığını ve fertilizasyon olayı esnasında meydana gelen olayların mekanizmalarını moleküler düzeyde literatür bilgileri ışığında derlemeyi amaçladık. Anahtar kelimeler: Fertilizasyon, kapasitasyon, akrozom reaksiyonu, sinyal proteinleri Abstract Fertilization, a complex sequence of interactions between the spermatozoon and the egg, is a highly complicated process. These events start with the release of a mature egg from the follicle, continue with the appearance of the two pronuclei after sperm entry, and are completed with the first mitotic divisions. This process, required for permanence of speciation in humans and all animals, has always attracted the attention of scientists. In our study we aim to compile which signaling networks take place in each stage of fertilization and the mechanism of the actions happened at molecular level during the fertilizations in the light of literature informatin. Key words: Fertilization, capacitation, acrosome reaction, signalling proteins
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Calcium is a universal messenger that mediates egg activation at fertilization in all sexually reproducing species studied. However, signaling pathways leading to calcium generation and the mechanisms of calcium-induced exit from meiotic arrest vary substantially among species. Here, we review the pathways of calcium signaling and the mechanisms of meiotic exit at fertilization in the eggs of the established developmental model, African clawed frog, Xenopus laevis. We also discuss calcium involvement in the early fertilization-induced events in Xenopus egg, such as membrane depolarization, the increase in intracellular pH, cortical granule exocytosis, cortical contraction, contraction wave, cortical rotation, reformation of the nuclear envelope, sperm chromatin decondensation and sister chromatid segregation.
    International Journal of Molecular Sciences 10/2014; 15(10):18659-18676. DOI:10.3390/ijms151018659 · 2.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cytoplasmic polyadenylation binding protein 1 (CPEB1) is a RNA binding protein, which regulates translation of target mRNAs by regulating polyadenylation status. CPEB1 plays important roles in the regulation of germline cell development by modulating cell cycle progression through the polyadenylation of target mRNAs such as cyclin B1. Similar mechanism is reported in proliferating astrocytes by us, although CPEB1 is involved in the transport of target mRNAs as well as local translation at dendritic spines. In this study, we found the expression of CPEB1 in cultured rat primary neural progenitor cells (NPCs). EGF stimulation of cultured NPCs induced rapid phosphorylation of CPEB1, a hallmark of CPEB1-dependent translational control along with cyclin B1 polyadenylation and translation. EGF-induced activation of ERK1/2 and Aurora A kinase was responsible for CPEB1 phosphorylation. Pharmacological inhibition studies suggested that ERK1/2 is involved in the activation of Aurora A kinase and regulation of CPEB1 phosphorylation in cultured NPCs. Long-term incubation in EGF resulted in the down-regulation of CPEB1 expression, which further increased expression of cyclin B1 and cell cycle progression. When we down-regulated the expression of CPEB1 in NPCs by siRNA transfection, the proliferation of NPCs was increased. Increased NPCs proliferation by down-regulation of CPEB1 resulted in eventual up-regulation of neuronal differentiation with increase in both pre- and post-synaptic proteins. The results from the present study may suggest the importance of translational control in the regulation of neuronal development, an emerging concept in many neurodevelopmental and psychiatric disorders such as autism spectrum disorder.
    Neurochemical Research 07/2013; DOI:10.1007/s11064-013-1102-4 · 2.55 Impact Factor


Available from