Down-regulation of the inositol 1,4,5-trisphosphate receptor in mouse eggs following fertilization or parthenogenetic activation.
Fertilization in mammalian eggs is characterized by the presence of intracellular calcium ([Ca(2+)]i) oscillations. In mouse eggs, these oscillations cease after a variable period of time and this is accompanied by a decrease in inositol 1,4,5-trisphosphate receptor (IP3R) responsiveness and down-regulation of the IP3R type 1 (IP3R-1). To investigate the signaling pathway responsible for inducing IP3R-1 down-regulation during fertilization, mouse eggs were exposed to or injected with several Ca(2+)-releasing agonists and the amounts of IP3R-1 immunoreactivity evaluated by Western blotting. Exposure to ethanol or ionomycin, which induce a single [Ca(2+)]i rise, failed to signal down-regulation of IP3R-1. However, [Ca(2+)]i oscillations induced by injection of boar sperm fractions (SF), which presumably stimulate production of IP3, or adenophostin A, an IP3R agonist, both induced down-regulation of IP3R-1 of a magnitude similar to or greater than that observed after fertilization. Exposure to thimerosal, an oxidizing agent that modifies the IP3R without stimulating production of IP3, also initiated down-regulation of IP3R-1, although oscillations initiated by SrCl(2) failed to evoke down-regulation of IP3R-1. The degradation of IP3R-1 in mouse eggs appears to be mediated by the proteasome pathway because it was inhibited by preincubation with lactacystin, a very specific proteasome inhibitor. We therefore suggest that persistent stimulation of the phosphoinositide pathway in mouse eggs by the sperm during fertilization or by injection of SF leads to down-regulation of the IP3R-1.
Jellerette
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Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts, 01003, USA.
He
C L
CL
Wu
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Parys
J B
JB
Fissore
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RA
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015536:Down-Regulation; D000431:Ethanol / Q000494:pharmacology; D005306:Fertilization / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism; D010063:Ovum / Q000502:physiology*; D010312:Parthenogenesis / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013094:Spermatozoa / Q000737:chemistry; D013324:Strontium / Q000494:pharmacology; D013347:Subcellular Fractions; D013552:Swine; D013849:Thimerosal / Q000494:pharmacology
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009097:Multienzyme Complexes; D018160:Receptors, Cytoplasmic and Nuclear; C085029:adenophostin A; D013849:Thimerosal; D000431:Ethanol; D015544:Inositol 1,4,5-Trisphosphate; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C025700:strontium chloride; D000241:Adenosine; D013324:Strontium