Regulation of inositol 1,4,5-trisphosphate receptor type 1 function during oocyte maturation by MPM-2 phosphorylation

Egg activation and further embryo development require a sperm-induced intracellular Ca2+ signal at the time of fertilization. Prior to fertilization, the egg's Ca2+ machinery is therefore optimized. To this end, during oocyte maturation, the sensitivity, i.e. the Ca2+ releasing ability, of the inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), which is responsible for most of this Ca2+ release, markedly increases. In this study, the recently discovered specific Polo-like kinase (Plk) inhibitor BI2536 was used to investigate the role of Plk1 in this process. BI2536 inactivates Plk1 in oocytes at the early stages of maturation and significantly decreases IP3R1 phosphorylation at an MPM-2 epitope at this stage. Moreover, this decrease in Plk1-dependent MPM-2 phosphorylation significantly lowers IP3R1 sensitivity. Finally, using in vitro phosphorylation techniques we identified T2656 as a major Plk1 site on IP3R1. We therefore propose that the initial increase in IP3R1 sensitivity during oocyte maturation is underpinned by IP3R1 phosphorylation at an MPM-2 epitope(s).