Fertilization stimulates long-lasting oscillations of CaMKII activity in mouse eggs

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Abstract

Elucidation of the biochemical mechanisms by which specific proteins transduce the all important intracellular calcium (Ca 2+ ) signal at fertilization into events of egg activation will increase our understanding of the regulation of the onset of development and the extent to which these signals can be experimentally modified. Previously, we reported data supporting the hypothesis that mouse eggs have the capability to generate oscillations of the activity of Ca 2+ and calmodulin-dependent kinase II (CaMKII), regulating the cell cycle and secretion. This study directly demonstrates transient increases of enzyme activity in relatively close synchrony with Ca 2+ oscillations for the first hour of fertilization in single mouse eggs monitored for both Ca 2+ and CaMKII activity. The extent of the enzyme activity increase was correlated with the level of intracellular Ca 2+ . After a rise in activity, the decrease in activity did not appear to be due to negative feedback from elevated Ca 2+ or CaMKII activity over time, since enzyme activity persisted after 8 min of elevated Ca 2+ from 7% ethanol activation. The contribution of CaMKII from a single sperm to the rise in CaMKII activity at fertilization appeared to be negligible. Also, long-term cell cycle inhibition was observed in fertilized eggs with the CaMKII antagonist myrAIP (50 μM), which did not inhibit the first large Ca 2+ transient or subsequent early oscillations but did reduce the percentage of eggs fertilized. Thus, mammalian eggs appear to drive many activation events over time to completion with repeated short bursts of Ca 2+ oscillation-dependent CaMKII activity, rather than by a steady-state, continuously elevated level of CaMKII activity that is maintained by periodic Ca 2+ oscillations. © 2004 Elsevier Inc. All rights reserved.

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Markoulaki, S., Matson, S., & Ducibella, T. (2004). Fertilization stimulates long-lasting oscillations of CaMKII activity in mouse eggs. Developmental Biology, 272(1), 15–25. https://doi.org/10.1016/j.ydbio.2004.04.008

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