Li Yu, Zhang Zihao, Zhang Yu, Xiong Bo
College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
Adv Sci (Weinh). 2025 Jul 2:e06639. doi: 10.1002/advs.202506639.
As a major component of the cytoskeleton, intermediate filaments are generally considered to play a supporting role in mitotic cells. They also take part in the regulation of cell motility, proliferation, differentiation, and apoptosis. However, their specific functions during meiosis are largely unknown. Here, a unique role of an intermediate filament protein beaded filament structural protein 2 (BFSP2) is reported, which is predominantly expressed in lens fiber epithelial cells, as a spindle formation controller in oocyte meiosis. BFSP2 is constantly expressed during oocyte meiotic maturation, and specifically distributed on the spindle apparatus at metaphase I (MI) and metaphase II (MII) stages. Depletion of BFSP2 resulted in the meiotic arrest at MI stage due to the aberrant spindle assembly-induced spindle assembly checkpoint activation. Depletion of BFSP2 also led to incorrect kinetochore-microtubule attachments and the occurrence of aneuploidy in oocytes. Mechanistically, immunoprecipitation combined with mass spectrometry analysis identified clathrin heavy chain 1 (CLTC) as the downstream mediator of BFSP2 during meiotic spindle assembly. It is further determined that BFSP2 recruited the molecular chaperone heat shock cognate protein 70 (HSC70) to the spindle apparatus for stabilizing CLTC, and thus driving the spindle formation. In summary, these findings uncover a noncanonical function of the intermediate filament protein BFSP2 as a spindle assembly controller in oocyte meiosis.
作为细胞骨架的主要组成部分，中间丝通常被认为在有丝分裂细胞中起支撑作用。它们还参与细胞运动、增殖、分化和凋亡的调控。然而，它们在减数分裂过程中的具体功能在很大程度上尚不清楚。在此，报道了一种中间丝蛋白珠状丝结构蛋白2（BFSP2）的独特作用，该蛋白主要在晶状体纤维上皮细胞中表达，作为卵母细胞减数分裂中的纺锤体形成控制器。BFSP2在卵母细胞减数分裂成熟过程中持续表达，并特异性地分布在减数第一次分裂中期（MI）和减数第二次分裂中期（MII）的纺锤体装置上。BFSP2的缺失导致减数第一次分裂期的减数分裂停滞，这是由于异常的纺锤体组装诱导纺锤体组装检查点激活所致。BFSP2的缺失还导致卵母细胞中动粒-微管连接错误和非整倍体的出现。机制上，免疫沉淀结合质谱分析确定网格蛋白重链1（CLTC）是减数分裂纺锤体组装过程中BFSP2的下游介质。进一步确定BFSP2将分子伴侣热休克同源蛋白70（HSC70）募集到纺锤体装置以稳定CLTC，从而驱动纺锤体形成。总之，这些发现揭示了中间丝蛋白BFSP2在卵母细胞减数分裂中作为纺锤体组装控制器的非经典功能。
