Filamin A is required for spindle migration and asymmetric division in mouse oocytes

Abstract

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. FASEB J. 31, 3677-3688 (2017

Tea polyphenol protects against cisplatin-induced meiotic defects in porcine oocytes

“…Expectedly, our data illustrated that DDP exposure decreased the acetylation level of α-tubulin, indicating that the loss of microtubule stability might be one of the major causes leading to the disorganized spindle structure. Additionally, the dynamics of actin filament, another indispensable component of cytoskeleton, has been reported to play important roles in spindle positioning and meiotic progression during oocyte meiosis [46–48]. Our findings validated that the perturbed actin polymerization might be another major reason resulting in the oocyte meiotic failure when exposed to DDP.…”

Effects of Short-Term Inhibition of Rho Kinase on Dromedary Camel Oocyte In Vitro Maturation

“…Moreover, TUBA1 increased with oocyte diameter, and CFLN increased with oocyte maturation and cumulus expansion, which supports the necessity of cytokinesis-related transcripts in the final stages of COC maturation. The resulting alterations and abnormalities in oocyte diameter and PB extrusion by RI are due to the direct effect of ROCK on tubulin and other cytoskeleton proteins' organization [31,42,44,[50][51][52][53][54][55][56]. Moreover, ZP thickness decreased with increasing RI supplementation duration.…”

“…However, it is important to note that spindle organization and polar body extrusion are not coordinated by a single gene. Many cytokinesis-related proteins, including actin, formin, profilin, cofilin, myosin, and tubulin, are effectors of the ROCK signaling pathway though which spindle positioning is regulated [43,[52][53][54][61][62][63][64]. Moreover, ROCK inhibitor increased cellular microtubule acetylation because ROCK regulates microtubule acetylation via phosphorylation of tubulin polymerization-promoting protein 1 [44,50].…”

CAP1-mediated actin cycling via ADF/cofilin proteins is essential for asymmetric division in mouse oocytes

“…Specifically, we observed the accumulation of excessive cytoplasmic actin mesh around spindles after CAP1 knockdown. The depletion of actin nucleators responsible for the formation of new actin filaments, such as FMN2 (Leader et al, 2002), SPIRE (Pfender et al, 2011) and the ARP2/3 complex (Sun et al, 2011b), or actin-binding proteins responsible for the maintenance of actin filaments, such as capping protein , tropomodulin (Jo et al, 2016), tropomyosin-3 (Jang et al, 2014) or filamin A (Wang et al, 2017) have been shown to impair asymmetric division by decreasing actin networks in oocytes. In contrast, excessive amounts of actin filaments in the cytoplasm have also been shown to be detrimental to spindle migrations, as seen with actin stabilization through GFP-UtrCH overexpression (Holubcová et al, 2013).…”

“…Because CAPs enhance the actin-severing activity of cofilin in vitro (Jansen et al, 2014), CAP1 knockdown in oocytes may complement excessive expression of active (S3A mutant) cofilin, which effectively decreases actin levels (Wang et al, 2017). We examined the amount of actin mesh under various conditions: CAP1 knockdown, constitutively active cofilin overexpression, and both CAP1 knockdown and cofilin overexpression.…”