Abstract
BackgroundDuring oocyte meiosis, the cytoskeleton dynamics, especially spindle organization, are critical for chromosome congression and segregation. However, the roles of the kinesin superfamily in this process are still largely unknown.ResultsIn the present study, Kif18a, a member of the kinesin-8 family, regulated spindle organization through its effects on tubulin acetylation in mouse oocyte meiosis. Our results showed that Kif18a is expressed and mainly localized in the spindle region. Knock down of Kif18a caused the failure of first polar body extrusion, dramatically affecting spindle organization and resulting in severe chromosome misalignment. Further analysis showed that the disruption of Kif18a caused an increase in acetylated tubulin level, which might be the reason for the spindle organization defects after Kif18a knock down in oocyte meiosis, and the decreased expression of deacetylase Sirt2 was found after Kif18a knock down. Moreover, microinjections of tubulin K40R mRNA, which could induce tubulin deacetylation, protected the oocytes from the effects of Kif18a downregulation, resulting in normal spindle morphology in Kif18a-knock down oocytes.ConclusionsTaken together, our results showed that Kif18a affected Sirt2-mediated tubulin acetylation level for spindle organization during mouse oocyte meiosis. Our results not only revealed the critical effect of Kif18a on microtubule stability, but also extended our understanding of kinesin activity in meiosis.
Highlights
During oocyte meiosis, the cytoskeleton dynamics, especially spindle organization, are critical for chro‐ mosome congression and segregation
The different stages of oocytes were examined by western blotting, which revealed that Kif18a is expressed at all stages during oocyte maturation (Fig. 1a)
The localization pattern of Kif18a indicates a relationship between Kif18a and the spindle region during mouse oocyte meiosis
Summary
The cytoskeleton dynamics, especially spindle organization, are critical for chro‐ mosome congression and segregation. The cytoskeleton, which is mainly constructed of microtubules and microfilaments, guarantees accurate chromosome congression, segregation and meiotic cell division [3, 20]. Free tubulins in the cytoplasm assemble and organize to form a meiotic spindle, which is involved in chromosome alignment and correct chromosome segregation during oocyte meiosis. During this process, post-translational modifications of tubulin The other is that kinesins are involved in spindle assembly and chromosome alignment in mitotic cells.
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