Cell cycle-dependent Ca2+ oscillations in mouse embryos are regulated by nuclear targeting of PLCzeta.
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; PLCzeta) that triggers Ca2+ oscillations similar to those caused by sperm. We show that PLCzeta-induced Ca2+ oscillations also occur exclusively during M phase. The cell cycle-dependency can be explained by PLCzeta's localisation to the pronuclei, which depends specifically upon a nuclear localisation signal sequence. Preventing pronuclear localisation of PLCzeta 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.
Larman
Mark G
MG
Department of Anatomy and Developmental Biology, University College London, WC1E 6BT, UK.
Saunders
Christopher M
CM
Carroll
John
J
Lai
F Anthony
FA
Swann
Karl
K
D019943:Amino Acid Substitution; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D019085:Fluorescent Antibody Technique, Direct; D005456:Fluorescent Dyes; D018507:Gene Expression Regulation, Developmental; D005973:Glutamine / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008845:Microinjections; D018613:Microscopy, Confocal; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism; D010312:Parthenogenesis; D054801:Phosphoinositide Phospholipase C; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D005456:Fluorescent Dyes; D005973:Glutamine; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; C499234:Plcz1 protein, mouse; D016650:Fluorescein-5-isothiocyanate; D002118:Calcium