title: Inositol 1,4,5-trisphosphate receptors are downregulated in mouse oocytes in response to sperm or adenophostin A but not to increases in intracellular Ca(2+) or egg activation.
abstract: Fertilization in mammals stimulates a series of Ca(2+) oscillations that continue for 3-4 h. Cell-cycle-dependent changes in the ability to release Ca(2+) are one mechanism that leads to the inhibition of Ca(2+) transients after fertilization. The downregulation of InsP(3)Rs at fertilization may be an additional mechanism for inhibiting Ca(2+) transients. In the present study we examine the mechanism of this InsP(3)R downregulation. We find that neither egg activation nor Ca(2+) transients are necessary or sufficient for the stimulation of InsP(3)R downregulation. First, parthenogenetic activation fails to stimulate downregulation. Second, downregulation persists when fertilization-induced Ca(2+) 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 InsP(3)Rs was microinjection of the potent InsP(3)R agonist adenophostin A. InsP(3)R 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 InsP(3)Rs. We show that sperm-induced Ca(2+) signaling is inhibited in such InsP(3)R-depleted eggs. These data show that InsP(3)R binding is sufficient for downregulation and that Ca(2+) signaling at fertilization is mediated via the InsP(3)R.
authors.affiliation: Department of Physiology, Department of Anatomy and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Brind
authors.forename: K
authors.initials: K
authors.lastname: Swann
authors.forename: J
authors.initials: J
authors.lastname: Carroll
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D051379:Mice; D009865:Oocytes / Q000502:physiology*; D010312:Parthenogenesis; D011480:Protease Inhibitors / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013084:Sperm-Ovum Interactions / Q000502:physiology*; D013324:Strontium / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011480:Protease Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C085029:adenophostin A; D000431:Ethanol; D004533:Egtazic Acid; D003513:Cycloheximide; D000241:Adenosine; D013324:Strontium