Study of Meiotic Kinetochore Regulation

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Our previous study suggests that MEIKIN is required for maintenance of centromeric cohesion in anaphase I like moa1 in fission yeast. We have shown that centromeric localization of Shugoshin-2 (Sgo2), the protector of centromeric cohesin in mouse meiosis, is diminished and it may explain precocious sister chromatids separation during anaphase I in MEIKIN KO (knockout). To investigate the cause of SGO2 localization decrease in Meikin-/- spermatocytes, we examined Bub1 which are known to regulate SGO2 localization.Since kinetochore enrichment of Plk1 largely depends on MEIKIN in meiosis, these results raised the possibility that Plk1 activity might be required for Bub1 localization at kinetochore in mouse meiosis. In Plk1 inhibited wild-type spermatocytes by BI 2536 treatment, centromeric Bub1 signals are diminished in metaphase I which coincide with MEIKIN KO whereas no significant effects could be seen in diakinesis.Next we examined that Mps1 regulation for Bub1 localization in wild-type spermatocytes which are treated with the Mps1 inhibitor Reversine. Indeed, Mps1 specifically regulated Bub1 in diakinesis and showed milder effect in metaphase I than Plk1 inhibition. Finally, simultaneous inhibition of both Plk1 and Mps1 reduced additional levels of Bub1 not only in diakinesis but also metaphase I. We conclude that MEIKIN dependent Plk1 may recruit Bub1 to the kinetochore in meiosis I that regulates SGO2 localization on centromere. Furthermore, Plk1 and Mps1 redundantly regulate Bub1 in meiosis I.