Li Yu, Zhang Hanwen, Zeng Wenjun, Miao Yilong, Sun Shaochen, Zhang Yu, Xiong Bo
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.
Adv Sci (Weinh). 2025 Jul;12(28):e2504066. doi: 10.1002/advs.202504066. Epub 2025 May 11.
The cytoskeleton is composed of microtubules, microfilaments, and intermediate filaments in cells. While the functions of microtubules and microfilaments have been well elucidated, the roles of intermediate filaments and associated proteins remain largely unknown, especially in meiosis. BFSP1 is an intermediate filament protein mainly expressed in the eye lens to play important roles in the development of congenital cataract. Here, we document that BFSP1 functions as a spindle regulator to drive the oocyte asymmetric division. Specifically, we found that BFSP1 distributed on the spindle apparatus during oocyte meiotic maturation. Depletion of BFSP1 resulted in symmetric division of oocytes, accompanied by the formation of elongated spindles at metaphase I and anaphase/telophase I stages. In addition, immunoprecipitation combined with mass spectrometry analysis identified MAP1B, a microtubule-associated protein, as an interacting partner of BFSP1. Depletion or mutation of MAP1B phenocopied the meiotic defects observed in BFSP1-depleted oocytes, and expression of exogenous MAP1B-EGFP in BFSP1-depleted oocytes recovered the spindle length and asymmetric division. We further determined that BFSP1 recruited molecular chaperone HSP90α on the spindle to stabilize MAP1B, thereby controlling the spindle length. To sum up, our findings reveal a unique meiotic role for BFSP1 in the regulation of spindle dynamics and oocyte asymmetric division.
细胞骨架由细胞内的微管、微丝和中间丝组成。虽然微管和微丝的功能已得到充分阐明,但中间丝及其相关蛋白的作用在很大程度上仍不清楚,尤其是在减数分裂过程中。BFSP1是一种主要在晶状体中表达的中间丝蛋白,在先天性白内障的发生发展中起重要作用。在此,我们证明BFSP1作为纺锤体调节因子驱动卵母细胞不对称分裂。具体而言,我们发现BFSP1在卵母细胞减数分裂成熟过程中分布于纺锤体装置上。BFSP1的缺失导致卵母细胞对称分裂,并在减数第一次分裂中期和后期/末期形成细长的纺锤体。此外,免疫沉淀结合质谱分析确定微管相关蛋白MAP1B是BFSP1的相互作用伴侣。MAP1B的缺失或突变模拟了在BFSP1缺失的卵母细胞中观察到的减数分裂缺陷,并且在BFSP1缺失的卵母细胞中外源表达MAP1B-EGFP可恢复纺锤体长度和不对称分裂。我们进一步确定BFSP1在纺锤体上招募分子伴侣HSP90α以稳定MAP1B,从而控制纺锤体长度。总之,我们的研究结果揭示了BFSP1在调节纺锤体动力学和卵母细胞不对称分裂方面独特的减数分裂作用。