Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation

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2005
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Rauh, Nadine R.
Schmidt, Andreas
Nigg, Erich A.
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Nature. 2005, 437(7061), pp. 1048-1052. ISSN 0028-0836. eISSN 1476-4687. Available under: doi: 10.1038/nature04093
Zusammenfassung

Vertebrate eggs awaiting fertilization are arrested at metaphase of meiosis II by a biochemical activity termed cytostatic factor (CSF). This activity inhibits the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase that triggers anaphase onset and mitotic/meiotic exit by targeting securin and M-phase cyclins for destruction. On fertilization a transient rise in free intracellular calcium causes release from CSF arrest and thus APC/C activation. Although it has previously been shown that calcium induces the release of APC/C from CSF inhibition through calmodulin-dependent protein kinase II (CaMKII), the relevant substrates of this kinase have not been identified. Recently, we characterized XErp1 (Emi2), an inhibitor of the APC/C and key component of CSF activity in Xenopus egg extract. Here we show that calcium-activated CaMKII triggers exit from meiosis II by sensitizing the APC/C inhibitor XErp1 for polo-like kinase 1 (Plx1)-dependent degradation. Phosphorylation of XErp1 by CaMKII leads to the recruitment of Plx1 that in turn triggers the destruction of XErp1 by phosphorylating a site known to serve as a phosphorylation-dependent degradation signal. These results provide a molecular explanation for how the fertilization-induced calcium increase triggers exit from meiosis II.

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie
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APC/C, metaphase II
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ISO 690RAUH, Nadine R., Andreas SCHMIDT, Jenny BORMANN, Erich A. NIGG, Thomas U. MAYER, 2005. Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation. In: Nature. 2005, 437(7061), pp. 1048-1052. ISSN 0028-0836. eISSN 1476-4687. Available under: doi: 10.1038/nature04093
BibTex
@article{Rauh2005-10-13Calci-14045,
  year={2005},
  doi={10.1038/nature04093},
  title={Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation},
  number={7061},
  volume={437},
  issn={0028-0836},
  journal={Nature},
  pages={1048--1052},
  author={Rauh, Nadine R. and Schmidt, Andreas and Bormann, Jenny and Nigg, Erich A. and Mayer, Thomas U.}
}
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