College of Animal Science & Technology, Nanjing Agricultural University, Nanjing, China.
J Cell Physiol. 2019 May;234(5):7492-7497. doi: 10.1002/jcp.27510. Epub 2018 Nov 27.
Intersectins (ITSNs) have been shown to act as adaptor proteins that govern multiple cellular events via regulating Cdc42 activity. However, it remains to be determined whether the ITSN-Cdc42 pathway is functional in porcine oocytes. To address this question, we used a small molecule, ZCL278, to selectively disrupt the ITSN2-Cdc42 interaction. In the present study, we find that porcine oocytes exposed to ZCL278 are unable to completely progress through meiosis. Meanwhile, the spindle defects and chromosomal congression failure are frequently detected in these oocytes. In support of this, we observed the accumulated distribution of vesicle-like ITSN2 signals around the chromosome/spindle region during porcine oocyte maturation. In addition, our results also showed that inhibition of the ITSN-Cdc42 interaction impairs the actin polymerization in porcine oocytes. In summary, the findings support a model where ITSNs, through the interaction with Cdc42, modulates the assembly of meiotic apparatus and actin polymerization, consequently ensuring the orderly meiotic progression during porcine oocyte maturation.
衔接蛋白（ITSNs）已被证明作为衔接蛋白，通过调节 Cdc42 活性来控制多种细胞事件。然而，ITSN-Cdc42 途径是否在猪卵母细胞中起作用仍有待确定。为了解决这个问题，我们使用了一种小分子 ZCL278 来选择性地破坏 ITSN2-Cdc42 相互作用。在本研究中，我们发现暴露于 ZCL278 的猪卵母细胞无法完全完成减数分裂。同时，这些卵母细胞中经常检测到纺锤体缺陷和染色体聚集中的失败。支持这一点，我们观察到在猪卵母细胞成熟过程中，囊泡样 ITSN2 信号在染色体/纺锤体区域周围的积累分布。此外，我们的结果还表明，抑制 ITSN-Cdc42 相互作用会损害猪卵母细胞中的肌动蛋白聚合。总之，这些发现支持了一种模型，即通过与 Cdc42 的相互作用，ITSNs 调节减数分裂装置的组装和肌动蛋白聚合，从而确保猪卵母细胞成熟过程中有序的减数分裂进行。
