M-Phase oscillations in PP1 activity are essential for accurate progression through mammalian oocyte meiosis

Abstract

Tightly controlled fluctuations in kinase and phosphatase activity play important roles in regulating M-Phase transitions. Protein Phosphatase 1 (PP1) is one of these phosphatases, with oscillations in PP1 activity driving mitotic M-Phase. Evidence from a variety of experimental systems also points to roles in meiosis. Here we report that PP1 is important for M-Phase transitions through mouse oocyte meiosis. We employed a unique small-molecule approach to inhibit or activate PP1 at distinct phases of mouse oocyte meiosis. These studies show that temporal control of PP1 activity is essential for G2/M transition, metaphase I/anaphase I transition, and the formation of a normal metaphase II oocyte. Our data also reveal that inappropriate activation of PP1 is more deleterious at G2/M transition than at prometaphase I-to-metaphase I, and that an active pool of PP1 during prometaphase is vital for metaphase I/anaphase I transition and metaphase II chromosome alignment. Taken together, these results establish that loss of oscillations in PP1 activity causes a range of severe meiotic defects, pointing to essential roles for PP1 in female fertility, and more broadly, M-Phase regulation. Summary statementAltering the normal cyclical activity of the phosphatase PP1 in oocytes causes a range of severe meiotic defects, pointing to essential roles for PP1 in M-Phase entry, progression, and exit.