Actin protects mammalian eggs against chromosome segregation errors

Actin protects mammalian eggs against chromosome segregation errors
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DOI:
10.1126/science.aal1647
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发表时间:
2017-08-25
期刊:
影响因子:
56.9
通讯作者:
Schuh, Melina
Schuh, Melina
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mogessie, Binyam;Schuh, Melina

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染色体分离是由微管组成的纺锤体驱动的,但通常被认为与肌动蛋白无关。在这里,我们报告了一种意想不到的动作蛋白依赖机制,该机制驱动哺乳动物卵子中染色体的精确排列和分离。在包括人类在内的几种哺乳动物的卵中,突出的肌动蛋白丝渗透在微管纺锤体中。在减数分裂I和II期间,破坏小鼠卵细胞中的肌动蛋白导致染色体错位数量和滞后染色体数量显著增加。我们发现肌动蛋白通过促进有功能的着丝点纤维(排列和分离染色体的微管束)的形成来驱动准确的染色体分离。因此,肌动蛋白对于防止卵子中的染色体分离错误至关重要,而染色体分离错误是导致流产、不孕和唐氏综合症的主要原因。
Chromosome segregation is driven by a spindle that is made of microtubules but is generally thought to be independent of actin. Here, we report an unexpected actin-dependent mechanism that drives the accurate alignment and segregation of chromosomes in mammalian eggs. Prominent actin filaments permeated the microtubule spindle in eggs of several mammalian species, including humans. Disrupting actin in mouse eggs led to significantly increased numbers of misaligned chromosomes as well as lagging chromosomes during meiosis I and II. We found that actin drives accurate chromosome segregation by promoting the formation of functional kinetochore fibers, the microtubule bundles that align and segregate the chromosomes. Thus, actin is essential to prevent chromosome segregation errors in eggs, which are a leading cause of miscarriages, infertility, and Down syndrome.