Cell cycle-dependent Ca2+ oscillations in mouse embryos are regulated by nuclear targeting of PLCzeta

J Cell Sci. 2004 May 15;117(Pt 12):2513-21. doi: 10.1242/jcs.01109.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Calcium / analysis
  • Calcium / metabolism*
  • Cell Cycle / physiology*
  • Cell Division
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • Embryo, Mammalian / metabolism*
  • Female
  • Fluorescein-5-isothiocyanate
  • Fluorescent Antibody Technique, Direct
  • Fluorescent Dyes
  • Gene Expression Regulation, Developmental*
  • Glutamine / metabolism
  • Mice
  • Mice, Inbred Strains
  • Microinjections
  • Microscopy, Confocal
  • Models, Biological
  • Oocytes / metabolism
  • Parthenogenesis
  • Phosphoinositide Phospholipase C
  • Type C Phospholipases / genetics
  • Type C Phospholipases / metabolism*

Substances

  • Fluorescent Dyes
  • Glutamine
  • Type C Phospholipases
  • Phosphoinositide Phospholipase C
  • Plcz1 protein, mouse
  • Fluorescein-5-isothiocyanate
  • Calcium