Lin Sheng-Li, Qi Shu-Tao, Sun Shao-Chen, Wang Ya-Peng, Schatten Heide, Sun Qing-Yuan
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Front Biosci (Elite Ed). 2010 Jun 1;2(4):1254-64. doi: 10.2741/e187.
P21-activated kinase 1 (PAK1), an effector of Rho GTPase Rac 1 and Cdc42, is required for mitotic progression. However, its functions in meiosis are unclear. In the present study, we examined the expression, localization and function of PAK1 during mouse oocyte meiotic maturation and found that PAK1 was mainly associated with the meiotic spindle microtubules. Taxol treatment resulted in localization of PAK1 on spindle and aster microtubules, while nocodazole treatment induced the dispersion of PAK1 protein into the cytoplasm. Loss-of-function of PAK1 by both inhibitor treatment and morpholino oligonucleotide injection caused disorganized spindles, decreased polar body extrusion and misaligned chromosomes. In addition, inhibition of PAK1 resulted in abnormal localization of mitogen-activated protein kinase kinase (MEK). Taken together, our results suggest that PAK1 plays an important role in spindle assembly and chromosome alignment during mouse oocyte meiotic maturation.
p21激活激酶1(PAK1)是Rho GTP酶Rac 1和Cdc42的效应器,是有丝分裂进程所必需的。然而,其在减数分裂中的功能尚不清楚。在本研究中,我们检测了PAK1在小鼠卵母细胞减数分裂成熟过程中的表达、定位和功能,发现PAK1主要与减数分裂纺锤体微管相关。紫杉醇处理导致PAK1定位于纺锤体和星体微管上,而诺考达唑处理则诱导PAK1蛋白分散到细胞质中。通过抑制剂处理和吗啉代寡核苷酸注射使PAK1功能丧失,导致纺锤体紊乱、极体排出减少和染色体排列错误。此外,抑制PAK1会导致丝裂原活化蛋白激酶激酶(MEK)定位异常。综上所述,我们的结果表明,PAK1在小鼠卵母细胞减数分裂成熟过程中的纺锤体组装和染色体排列中起重要作用。