Ma Rujun, Hou Xiaojing, Zhang Liang, Sun Shao-Chen, Schedl Tim, Moley Kelle, Wang Qiang
College of Veterinary Medicine and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; and.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; and.
FASEB J. 2014 Sep;28(9):4026-35. doi: 10.1096/fj.14-250886. Epub 2014 May 29.
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.
Rab GTP酶是囊泡运输途径中高度保守的成分。Rab5作为内吞运输的主要调节因子，已被证明在膜拴系和对接中发挥作用。然而，Rab5在减数分裂中的功能尚未得到研究。在此，我们报告在小鼠卵母细胞中特异性敲低Rab5a后，出现了纺锤体拉长和染色体排列紊乱，伴有动粒-微管错误附着的现象。此外，在Rab5a敲低后的中期卵母细胞中，核基质成分着丝粒蛋白F（CENPF）在动粒处的定位和水平严重降低。与此发现一致的是，在Rab5a缺失的卵母细胞中，从前期阻滞到减数分裂I的转变过程中核纤层的解体也受到损害。值得注意的是，卵母细胞特异性敲除CENPF可模拟Rab5a敲低导致的减数分裂缺陷。总之，我们的数据支持这样一种模型，即Rab5a阳性囊泡可能通过与核纤层相互作用，调节着丝粒处CENPF的定位和水平，从而确保减数分裂卵母细胞中纺锤体长度合适以及动粒-微管附着正确。
