INHIBITION OF PROTEIN-KINASES BY 6-DIMETHYLAMINOPURINE ACCELERATES THE TRANSITION TO INTERPHASE IN ACTIVATED MOUSE OOCYTES

Mouse oocyte activation is followed by a peculiar period during which the interphase network of microtubules does not form and the chromosom es remain condensed despite the inactivation of MPF. To evaluate the r ole of protein phosphorylation during this period, we studied the effe cts of the protein kinase inhibitor 6-dimethylaminopurine (6-DMAP) on fertilization and/or parthenogenetic activation of metaphase II-arrest ed mouse oocytes. 6-DMAP by itself does not induce the inactivation of histone H1 kinase in metaphase II-arrested oocytes, and does not infl uence the dynamics of histone H1 kinase inactivation during oocyte act ivation. However, 6-DMAP inhibits protein phosphorylation after oocyte activation. In addition, the phosphorylated form of some proteins dis appear earlier in oocytes activated in the_presence of 6-DMAP than in the activated control oocytes. This is correlated with the acceleratio n of some post-fertilization morphological events, such as sperm chrom atin decondensation and its transient recondensation, formation of the interphase network of microtubules and pronuclear formation. In addit ion, numerous abnormalities could be observed: (1) the spindle rotatio n and polar body extrusion are inhibited; (2) the exchange of protamin es into histones seems to be impaired, as judged by the morphology of DNA fibrils by electron microscopy; (3) the formation of a new nuclear envelope around the sperm chromatin proceeds prematurely, while recon densation is not yet completed. These observations suggest that the 6- DMAP-sensitive kinase(s) is (are) involved in the control of post-fert ilization events such as the formation of the interphase network of mi crotubules, the remodelling of sperm chromatin and pronucleus formatio n.