Wang HaiYang, Guo Jing, Lin ZiLi, Namgoong Suk, Oh Jeong Su, Kim Nam-Hyung
Department of Animal Sciences, Chungbuk National University, Cheongju, South Korea.
School of Life Sciences, Tsinghua University, Beijing, China.
FASEB J. 2017 Aug;31(8):3677-3688. doi: 10.1096/fj.201700056R. Epub 2017 May 9.
Dynamic changes in the actin network are crucial for the cortical migration of spindles and establishment of polarity, to ensure asymmetric division during meiotic maturation. In this study, filamin A (FLNA) was found to be an essential actin regulator that controlled spindle migration and asymmetric division during oocyte meiosis. FLNA was localized in the cytoplasm and enriched at the cortex and near the chromosomes. Knockdown of FLNA impaired meiotic asymmetric division and spindle migration with a decrease in the amount of cytoplasmic actin mesh and cortical actin levels. Moreover, FLNA knockdown reduced the phosphorylation of cofilin and Rho kinase (ROCK) near the spindle. Similar phenotypes, such as decreased filament actin levels, impaired spindle migration and polar body extrusion, were observed when active cofilin (S3A) was overexpressed or ROCK was inhibited. Notably, we found that FLNA and ROCK interacted directly in mouse oocytes. Taken together, our results show that FLNA plays crucial roles in asymmetric division during meiotic maturation by regulating ROCK-cofilin-mediated actin reorganization.-Wang, H., Guo J., Lin, Z., Namgoong, S., Oh, J. S., Kim, N.-H. Filamin A is required for spindle migration and asymmetric division in mouse oocytes.
肌动蛋白网络的动态变化对于纺锤体的皮质迁移和极性建立至关重要，以确保减数分裂成熟过程中的不对称分裂。在本研究中，发现细丝蛋白A（FLNA）是一种重要的肌动蛋白调节因子，它在卵母细胞减数分裂过程中控制纺锤体迁移和不对称分裂。FLNA定位于细胞质中，并在皮质和染色体附近富集。敲低FLNA会损害减数分裂不对称分裂和纺锤体迁移，同时细胞质肌动蛋白网的数量和皮质肌动蛋白水平降低。此外，敲低FLNA会降低纺锤体附近的丝切蛋白和Rho激酶（ROCK）的磷酸化水平。当活性丝切蛋白（S3A）过表达或ROCK被抑制时，会观察到类似的表型，如丝状肌动蛋白水平降低、纺锤体迁移受损和极体排出受损。值得注意的是，我们发现FLNA和ROCK在小鼠卵母细胞中直接相互作用。综上所述，我们的结果表明，FLNA通过调节ROCK-丝切蛋白介导的肌动蛋白重组，在减数分裂成熟过程中的不对称分裂中发挥关键作用。-王，H.，郭J.，林，Z.，南宫，S.，吴，J.S.，金，N.-H.细丝蛋白A是小鼠卵母细胞纺锤体迁移和不对称分裂所必需的。
