Rab5a is required for spindle length control and kinetochore-microtubule attachment during meiosis in oocytes
Rab5a is required for spindle length control and kinetochore-microtubule attachment during meiosis in oocytes
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DOI：
10.1096/fj.14-250886
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发表时间：
2014-09-01
期刊：
影响因子：
4.8
通讯作者：
Wang, Qiang
中科院分区：
文献类型：
--
作者：
Ma, Rujun;Hou, Xiaojing;Wang, Qiang
Rab gtp酶是囊泡运输途径的高度保守成分。Rab5作为内吞运输的主要调节因子，已被证明在膜系固和对接中起作用。然而，Rab5在减数分裂中的作用尚未明确。在这里，我们报告了细长纺锤体和染色体错位，与着丝点微管错误附着，在小鼠卵母细胞中Rab5a的特异性耗尽。此外，在Rab5a敲除后，中期卵母细胞中着丝点的着丝粒蛋白F （CENPF）的定位和水平严重降低。着丝粒蛋白F是核基质的一个组成部分。与这一发现一致的是，在rab5a缺失的卵母细胞中，从前期停滞到减数分裂I的过渡过程中核层的拆卸也受到了损害。值得注意的是，对CENPF的卵母细胞特异性消融会引起Rab5a敲低导致的减数分裂缺陷。总之，我们的数据支持一个模型，rab5a阳性囊泡可能通过与核层的相互作用，调节着丝粒的CENPF定位和水平，从而确保减数分裂卵母细胞中适当的纺锤体长度和着丝点-微管附着。
Rab GTPases are highly conserved components of vesicle trafficking pathways. Rab5, as a master regulator of endocytic trafficking, has been shown to function in membrane tethering and docking. However, the function of Rab5 in meiosis has not been addressed. Here, we report elongated spindles and misaligned chromosomes, with kinetochore-microtubule misattachments, on specific depletion of Rab5a in mouse oocytes. Moreover, the localization and levels of centromere protein F (CENPF), a component of the nuclear matrix, are severely reduced at kinetochores in metaphase oocytes following Rab5a knockdown. Consistent with this finding, nuclear lamina disassembly in the transition from prophase arrest to meiosis I is also impaired in Rab5a-depleted oocytes. Notably, oocyte-specific ablation of CENPF phenocopies the meiotic defects resulting from Rab5a knockdown. In summary, our data support a model where Rab5a-positive vesicles, likely through interaction with nuclear lamina, modulate CENPF localization and levels at centromeres, consequently ensuring proper spindle length and kinetochore-microtubule attachment in meiotic oocytes.