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First published online May 24, 2004
doi: 10.1242/10.1242/jcs.01109

Journal of Cell Science 117, 2513-2521 (2004)
Published by The Company of Biologists 2004
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Research Article

Cell cycle-dependent Ca2+ oscillations in mouse embryos are regulated by nuclear targeting of PLC{zeta}

Mark G. Larman1,2, Christopher M. Saunders2, John Carroll3, F. Anthony Lai2 and Karl Swann1,*

1 Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, UK
2 Cell Signalling Laboratory, Wales Heart Research Institute, University of Wales College of Medicine, Cardiff, CF14 4XN, UK
3 Department of Physiology, University College London, London, WC1E 6BT, UK

* Author for correspondence (e-mail: k.swann{at}ucl.ac.uk)

Accepted 19 January 2004

During the first cell cycle Ca2+ oscillations are regulated in a cell cycle-dependent manner, such that the oscillations are unique to M phase. How the Ca2+ oscillations are regulated with such cell cycle stage-dependency is unknown, despite their importance for egg activation and embryo development. We recently identified a novel, sperm-specific phospholipase C (PLCzeta; PLC{zeta}) that triggers Ca2+ oscillations similar to those caused by sperm. We show that PLC{zeta}-induced Ca2+ oscillations also occur exclusively during M phase. The cell cycle-dependency can be explained by PLC{zeta}'s localisation to the pronuclei, which depends specifically upon a nuclear localisation signal sequence. Preventing pronuclear localisation of PLC{zeta} by mutation of the nuclear localisation signal, or by inhibiting pronuclear formation/import, can prolong Ca2+ oscillations or allow them to occur during interphase. These data suggest a novel mechanism for regulating a PLC through nuclear sequestration and may explain the cell cycle-dependent regulation of Ca2+ oscillations following fertilisation.

Key words: Fertilisation, Phospholipase C, Ca2+ oscillations, Cell cycle


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