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PAK4 在小鼠卵母细胞减数分裂成熟过程中调节肌动蛋白和微管动力学。

PAK4 Regulates Actin and Microtubule Dynamics during Meiotic Maturation in Mouse Oocyte.

机构信息

College of Animal Science and Technology, College of Life Sciences, Institute of Reproductive Science, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao 266109, China.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Int J Biol Sci. 2019 Sep 7;15(11):2408-2418. doi: 10.7150/ijbs.34718. eCollection 2019.

Abstract

Meiotic maturation of oocyte is an important process for successful fertilization, in which cytoskeletal integrality takes a significant role. The p-21 activated kinases (PAKs) belong to serine/threonine kinases that affect wide range of processes that are crucial for cell motility, survival, cell cycle, and proliferation. In this study, we used a highly selective inhibitor of PAK4, PF-3758309, to investigate the functions of PAK4 during meiotic maturation of mouse oocytes. We found that PAK4 inhibition resulted in meiotic arrest by inducing abnormal microfilament and microtubule dynamics. PAK4 inhibition impaired the microtubule stability and led to the defective kinetochore-microtubule (K-M) attachment which inevitably resulted in aneuploidy. Also, PAK4 inhibition induced abnormal acentriolar centrosome assembly during meiotic maturation. In conclusion, all these combined results suggest that PAK4 is necessary for the oocyte meiosis maturation as a regulator of cytoskeleton.

摘要

卵母细胞减数分裂成熟是受精成功的重要过程,其中细胞骨架的完整性起着重要作用。p21 激活激酶(PAKs)属于丝氨酸/苏氨酸激酶,影响细胞运动、存活、细胞周期和增殖等广泛过程。在这项研究中,我们使用了一种高度选择性的 PAK4 抑制剂 PF-3758309,来研究 PAK4 在小鼠卵母细胞减数分裂成熟过程中的作用。我们发现,PAK4 抑制通过诱导异常的微丝和微管动力学导致减数分裂阻滞。PAK4 抑制破坏了微管的稳定性,导致动粒-微管(K-M)连接的缺陷,不可避免地导致非整倍体。此外,PAK4 抑制诱导减数分裂成熟过程中中心体异常形成。总之,这些综合结果表明 PAK4 作为细胞骨架的调节剂,对于卵母细胞减数分裂成熟是必需的。

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