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First published online October 22, 2008
doi: 10.1242/10.1242/jcs.036855

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Across the meiotic divide – CSF activity in the post-Emi2/XErp1 era

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA

View larger version (12K): [in this window] [in a new window]   Fig. 1. The process of oocyte maturation. The maturation process is driven by multiple factors, including Cdc2–cyclin-B, Mos protein and Emi2 protein, the relative levels of which throughout the maturation process are illustrated. Xenopus oocytes are arrested in G2. Upon progesterone treatment, oocytes enter meiosis I (MI). Oocytes then transit directly from meiosis I to meiosis II (MII), without an intervening interphase, and arrest at MII (when they are termed eggs), often for prolonged periods of time. Only upon fertilization will the eggs exit MII and commence rapid embryonic cell divisions.

View larger version (19K): [in this window] [in a new window]   Fig. 2. Mos and the APC/C in the regulation of CSF activity. (A) The Mos pathway, which includes the apical kinase Mos and the downstream kinases MEK, MAPK and Rsk, was shown to be crucial for CSF arrest. However, the link between Rsk and CSF required clarification. (B) CSF was manifested as an inhibition of the APC/C and stabilization of Cdc2–cyclin-B. (C) Taking A and B together, it was postulated that Rsk might work through the APC/C to regulate CSF. However, the link between Rsk and the APC/C was initially unclear.

View larger version (10K): [in this window] [in a new window]   Fig. 3. Fertilization-mediated Emi2 degradation and CSF release. CSF arrest is controlled by Emi2-mediated APC/C inhibition. Upon fertilization, CaMKII kinase activity increases, leading to Emi2 phosphorylation, which creates a Plx1-binding motif on Emi2. Emi2-bound Plx1 then phosphorylates Emi2, allowing Emi2 to be recognized by the β-TrCP E3 ubiquitin ligase. Emi2 ubiquitylation primes Emi2 for degradation, leading to APC/C activation and, eventually, exit from CSF arrest.

View larger version (14K): [in this window] [in a new window]   Fig. 4. Emi2 links the Mos pathway and the APC/C to regulate CSF. The ability of Emi2 to bind and inhibit the APC/C is modulated by Cdc2–cyclin-B-mediated phosphorylation. Specifically, phosphorylation at the Emi2 C-terminus weakens the Emi2-APC/C interaction, promoting dissociation of the Emi2-APC/C complex and activation of APC/C. During CSF arrest, Cdc2–cyclin-B-mediated Emi2 phosphorylation is antagonized by the Mos-MAPK pathway. The Mos pathway promotes recruitment of PP2A to Emi2, keeping Emi2 dephosphorylated. This allows Emi2 activation and APC/C inhibition. Bound PP2A can also promote Emi2 stabilization by dephosphorylating Emi2 at its N-terminus – otherwise, Cdc2–cyclin-B-mediated phosphorylation at this terminus would trigger Emi2 ubiquitylation and degradation. The Mos pathway therefore works through Emi2 to modulate APC/C activity, providing a link between Mos and the APC/C to regulate CSF arrest.

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