Abstract
Dynamic actin reorganization is the main driving force for spindle migration and asymmetric cell division in mammalian oocytes. It has been reported that various actin nucleators including Formin-2 are involved in the polarization of the spindle and in asymmetric cell division. In mammals, the formin family is comprised of 15 proteins. However, their individual roles in spindle migration and/or asymmetric division have not been elucidated yet. In this study, we employed a newly developed inhibitor for formin family proteins, small molecule inhibitor of formin homology 2 domains (SMIFH2), to assess the functions of the formin family in mouse oocyte maturation. Treatment with SMIFH2 during in vitro maturation of mouse oocytes inhibited maturation by decreasing cytoplasmic and cortical actin levels. In addition, treatment with SMIFH2, especially at higher concentrations (500 μM), impaired the proper formation of meiotic spindles, indicating that formins play a role in meiotic spindle formation. Knockdown of the mDia2 formins caused a similar decrease in oocyte maturation and abnormal spindle morphology, mimicking the phenotype of SMIFH2-treated cells. Collectively, these results suggested that besides Formin-2, the other proteins of the formin, including mDia family play a role in asymmetric division and meiotic spindle formation in mammalian oocytes.
Highlights
During meiosis I, mammalian oocytes undergo transitions via various stages of cell cycle[1]
Maturation was nearly abolished after treatment with SMIFH2 for 0–8 h followed by continued maturation without SMIFH2, indicating that SMIFH2 treatment after germinal vesicle breakdown (GVBD) is crucial for full inhibition of oocyte maturation
These results suggested that the inhibitory effect of SMIFH2 on oocyte maturation takes effect after the GVBD-metaphase I (MI) transition
Summary
During meiosis I, mammalian oocytes undergo transitions via various stages of cell cycle[1]. Various actin nucleators, including Formin-2[7,8,9], Spire[10] and the Arp2/3 complex[11, 12], play essential roles in the asymmetric migration of the spindle by promoting the formation of new actin filaments. Actin-binding proteins including tropomyosin[18] and actin capping protein[19] play important roles in oocyte maturation by regulating the stability and growth of the actin filaments. Because there are more than 100 different types of actin-binding proteins in mammals, most of them playing crucial roles in the formation and maintenance of the actin cytoskeleton[20, 21], many actin-binding proteins have been hypothesized to have an important function in oocyte maturation. The exact roles of many actin-binding proteins including actin nucleators in the asymmetric division of oocytes have not been elucidated till date
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