Calmodulin-dependent protein kinase gamma 3 (CamKIIγ3) mediates the cell cycle resumption of metaphase II eggs in mouse

Mature mammalian eggs are ovulated arrested at meiotic metaphase II. Sperm break this arrest by an oscillatory Ca2+ signal that is necessary and sufficient for the two immediate events of egg activation: cell cycle resumption and cortical granule release. Previous work has suggested that cell cycle resumption, but not cortical granule release, is mediated by calmodulin-dependent protein kinase II (CamKII). Here we find that mouse eggs contain detectable levels of only one CamKII isoform, gamma 3. Antisense morpholino knockdown of CamKII gamma 3 during oocyte maturation produces metaphase II eggs that are insensitive to parthenogenetic activation by Ca2+ stimulation and insemination. The effect is specific to this morpholino, as a 5-base-mismatch morpholino is without effect, and is rescued by CamKII gamma 3 or constitutively active CamKII cRNAs. Although CamKII-morpholino-treated eggs fail to exit metaphase II arrest, cortical granule exocytosis is not blocked. Therefore, CamKII gamma 3 plays a necessary and sufficient role in transducing the oscillatory Ca2+ signal into cell cycle resumption, but not into cortical granule release.