Title: Cell cycle-coupled [Ca2+]i oscillations in mouse zygotes and function of the inositol 1,4,5-trisphosphate receptor-1
Authors: Jellerette, Teru ×
Kurokawa, Manabu
Lee, Bora
Malcuit, Chris
Yoon, Sook-Young
Smyth, Jeremy
Vermassen, Elke
De Smedt, Humbert
Fissore, Rafael A
Parys, Jan #
Issue Date: Oct-2004
Publisher: Academic press inc elsevier science
Series Title: Developmental Biology vol:274 issue:1 pages:94-109
Abstract: Sperm entry in mammalian eggs initiates oscillations in the concentration of free calcium ([Ca(2+)](i)). In mouse eggs, oscillations start at metaphase II (MII) and conclude as the zygotes progress into interphase and commence pronuclear (PN) formation. The inositol 1,4,5-trisphosphate receptor (IP(3)R-1), which underlies the oscillations, undergoes degradation during this transition, suggesting that one or more of the eggs' Ca(2+)-releasing machinery components may be regulated in a cell cycle-dependent manner, thereby coordinating [Ca(2+)](i) responses with the cell cycle. To ascertain the site(s) of interaction, we initiated oscillations at different stages of the cell cycle in zygotes with different IP(3)R-1 mass. In addition to sperm, we used two other agonists: porcine sperm factor (pSF), which stimulates production of IP(3), and adenophostin A, a non-hydrolyzable analogue of IP(3). None of the agonists tested induced oscillations at interphase, suggesting that neither decreased IP(3)R-1 mass nor lack of production or excessive IP(3) degradation can account for the insensitivity to IP(3) at this stage. Moreover, the releasable Ca(2+) content of the stores did not change by interphase, but it did decrease by first mitosis. More importantly, experiments revealed that IP(3)R-1 sensitivity and possibly IP(3) binding were altered at interphase, and our data demonstrate stage-specific IP(3)R-1 phosphorylation by M-phase kinases. Accordingly, increasing the activity of M-phase kinases restored the oscillatory-permissive state in zygotes. We therefore propose that the restriction of oscillations in mouse zygotes to the metaphase stage may be coordinated at the level of IP(3)R-1 and that this involves cell cycle stage-specific receptor phosphorylation.
ISSN: 0012-1606
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Toxicology and Pharmacology
Laboratory of Molecular and Cellular Signaling
Physiology Section (-)
× corresponding author
# (joint) last author

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