Inositol 1,4,5-trisphosphate receptors are downregulated in mouse oocytes in response to sperm or adenophostin A but not to increases in intracellular Ca2+ or egg activation

Sophie Brind, Karl Swann, John Carroll

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104 Citations (Scopus)

Abstract

Fertilization in mammals stimulates a series of Ca2+ oscillations that continue for 3-4 h. Cell-cycle-dependent changes in the ability to release Ca2+ are one mechanism that leads to the inhibition of Ca2+ transients after fertilization. The downregulation of InsP3Rs at fertilization may be an additional mechanism for inhibiting Ca2+ transients. In the present study we examine the mechanism of this InsP3R downregulation. We find that neither egg activation nor Ca2+ transients are necessary or sufficient for the stimulation of InsP3R downregulation. First, parthenogenetic activation fails to stimulate downregulation. Second, downregulation persists when fertilization-induced Ca2+ transients and egg activation are inhibited using BAPTA. Third, downregulation can be induced in immature oocytes that do not undergo egg activation. Other than fertilization, the only stimulus that downregulated InsP3Rs was microinjection of the potent InsP3R agonist adenophostin A. InsP3R downregulation was inhibited by the cysteine protease inhibitor ALLN but MG132 and lactacystin were not effective. Finally, we have injected maturing oocytes with adenophostin A and produced MII eggs depleted of InsP3Rs. We show that sperm-induced Ca2+ signaling is inhibited in such InsP3R-depleted eggs. These data show that InsP3R binding is sufficient for downregulation and that Ca2+ signaling at fertilization is mediated via the InsP3R. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)251-265
Number of pages15
JournalDevelopmental Biology
Volume223
Issue number2
DOIs
Publication statusPublished - 15 Jul 2000
Externally publishedYes

Keywords

  • Adenophostin
  • Calcium
  • Fertilization
  • In vitro maturation
  • Inositol 1,4,5-trisphosphate
  • Oocyte
  • Proteolysis

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