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EMBO Rep. 2018 Oct 29. pii: e46433. doi: 10.15252/embr.201846433. [Epub ahead of print]

Calcineurin promotes APC/C activation at meiotic exit by acting on both XErp1 and Cdc20.

Author information

1
Department of Biology, University of Konstanz, Konstanz, Germany.
2
Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany.
3
MRC Laboratory of Molecular Biology, Cambridge, UK.
4
Department of Biology, University of Konstanz, Konstanz, Germany thomas.u.mayer@uni-konstanz.de.

Abstract

Vertebrate oocytes await fertilization arrested at metaphase of the second meiotic division. Fertilization triggers a transient calcium wave, which induces the activation of the anaphase-promoting complex/cyclosome (APC/C) and its co-activator Cdc20 resulting in the destruction of cyclin B and hence meiotic exit. Two calcium-dependent enzymes are implicated in fertilization-induced APC/CC dc20 activation: calcium-/calmodulin-dependent kinase type II (CaMKII) and calcineurin (CaN). While the role of CaMKII in targeting the APC/C inhibitor XErp1/Emi2 for destruction is well-established, it remained elusive how CaN affects APC/CC dc20 activation. Here, we discover that CaN contributes to APC/CC dc20 activation in Xenopus laevis oocytes by two independent but interrelated mechanisms. First, it facilitates the degradation of XErp1 by dephosphorylating it at a site that is part of a phosphorylation-dependent recruiting motif for PP2A-B'56, which antagonizes inhibitory phosphorylation of XErp1. Second, it dephosphorylates Cdc20 at an inhibitory site, thereby supporting its APC/C-activating function. Thus, our comprehensive analysis reveals that CaN contributes to timely APC/C activation at fertilization by both negatively regulating the APC/C inhibitory activity of XErp1 and positively regulating the APC/C-activating function of Cdc20.

KEYWORDS:

Xenopus laevis ; APC/C; Calcineurin; Cdc20; Meiosis; XErp1

PMID:
30373936
DOI:
10.15252/embr.201846433

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