Shan Meng-Meng, Lu Ping-Shuang, Zou Yuan-Jing, Zhang Kun-Huan, Liu Jing-Cai, Ju Jia-Qian, Sun Shao-Chen
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
J Cell Sci. 2025 Jul 15;138(14). doi: 10.1242/jcs.264015. Epub 2025 Jul 22.
Meiotic spindle organization and cytokinesis are important for mammalian oocyte maturation. CLIP-associating protein 1 (CLASP1) is a member of the microtubule plus-end-binding proteins that has been reported to regulate cytokinesis in mitosis; however, the functions of CLASP1 in meiosis are still unclear. In this study, we found that CLASP1 plays critical roles both at metaphase and telophase in mouse oocyte meiosis. Our results indicated that CLASP1 is essential for oocyte maturation. Its knockdown caused spindle organization defects and microtubule-kinetochore-attachment defects at metaphase I, which might be due to its association with polo-like kinase 1 (PLK1) and/or phosphorylated mitogen-activated protein kinases (MAPKs), specifically phosphorylated MAPK1 and MAPK3. Furthermore, the levels of deacetylases, i.e. histone deacetylase 6 (HDAC6) and/or NAD-dependent protein deacetylase sirtuin-1 (SIRT1), were found to be increased, which further affected tubulin acetylation levels and microtubule stability after CLASP1 knockdown. We also showed that CLASP1 can associate with PLK1 and/or protein regulator of cytokinesis 1 (PRC1)-based central spindle formation and cytokinesis at telophase I. Moreover, cytoplasmic dynein 1 intermediate chain 1 (DYNC1I1) was recognized to interact closely with CLASP1 and may function as a downstream motor protein involved in the orderly transport of PLK1. Taken together, we demonstrated that CLASP1 may associate with DYNC1I1 to play multiple roles in PLK1-mediated spindle organization and cytokinesis in mouse oocyte meiosis.
减数分裂纺锤体组织和胞质分裂对于哺乳动物卵母细胞成熟至关重要。CLIP相关蛋白1（CLASP1）是微管正端结合蛋白家族的成员，据报道其在有丝分裂中调节胞质分裂；然而，CLASP1在减数分裂中的功能仍不清楚。在本研究中，我们发现CLASP1在小鼠卵母细胞减数分裂的中期和末期均发挥关键作用。我们的结果表明CLASP1对卵母细胞成熟至关重要。其敲低导致减数分裂中期I纺锤体组织缺陷和微管 - 动粒附着缺陷，这可能是由于其与polo样激酶1（PLK1）和/或磷酸化的丝裂原活化蛋白激酶（MAPK），特别是磷酸化的MAPK1和MAPK3相关。此外，发现去乙酰化酶，即组蛋白去乙酰化酶6（HDAC6）和/或NAD依赖性蛋白去乙酰化酶沉默调节蛋白1（SIRT1）的水平升高，这在CLASP1敲低后进一步影响微管蛋白乙酰化水平和微管稳定性。我们还表明CLASP1可以与PLK1和/或基于胞质分裂蛋白调节剂1（PRC1）的中央纺锤体形成以及减数分裂末期I的胞质分裂相关。此外，细胞质动力蛋白1中间链1（DYNC1I1）被认为与CLASP1密切相互作用，并且可能作为参与PLK1有序运输的下游运动蛋白发挥作用。综上所述，我们证明CLASP1可能与DYNC1I1相关联，在小鼠卵母细胞减数分裂中PLK1介导的纺锤体组织和胞质分裂中发挥多种作用。
