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中间丝蛋白BFSP1通过调节纺锤体长度维持卵母细胞不对称分裂。

Intermediate Filament Protein BFSP1 Maintains Oocyte Asymmetric Division by Modulating Spindle Length.

作者信息

Li Yu, Zhang Hanwen, Zeng Wenjun, Miao Yilong, Sun Shaochen, Zhang Yu, Xiong Bo

机构信息

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.

College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.

出版信息

Adv Sci (Weinh). 2025 Jul;12(28):e2504066. doi: 10.1002/advs.202504066. Epub 2025 May 11.

DOI:10.1002/advs.202504066
PMID:40349178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12302563/
Abstract

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.

摘要

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。

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本文引用的文献

1
Mechanics of Single Cytoskeletal Filaments.单条细胞骨架细丝的力学原理。
Annu Rev Biophys. 2025 May;54(1):303-327. doi: 10.1146/annurev-biophys-030722-120914. Epub 2025 Feb 10.
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Vimentin and Desmin Intermediate Filaments Maintain Mitochondrial Membrane Potential.波形蛋白和结蛋白中间丝维持线粒体膜电位。
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Mouse polyomavirus infection induces lamin reorganisation.小鼠多瘤病毒感染会引发核纤层蛋白重排。
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5
Predicting Infertility: How Genetic Variants in Oocyte Spindle Genes Affect Egg Quality.预测不孕:卵母细胞纺锤体基因中的遗传变异如何影响卵子质量。
Adv Anat Embryol Cell Biol. 2024;238:1-22. doi: 10.1007/978-3-031-55163-5_1.
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Colonocyte keratins stabilize mitochondria and contribute to mitochondrial energy metabolism.结肠细胞角蛋白稳定线粒体并有助于线粒体能量代谢。
Am J Physiol Gastrointest Liver Physiol. 2024 Sep 1;327(3):G438-G453. doi: 10.1152/ajpgi.00220.2023. Epub 2024 Jun 11.
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Structural determinants of intermediate filament mechanics.中间丝力学的结构决定因素。
Curr Opin Cell Biol. 2024 Aug;89:102375. doi: 10.1016/j.ceb.2024.102375. Epub 2024 Jun 7.
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Lens Cytoskeleton: An Update on the Etiopathogenesis of Human Cataracts.晶状体细胞骨架:人类白内障病因发病机制的最新进展
Cureus. 2024 Mar 23;16(3):e56793. doi: 10.7759/cureus.56793. eCollection 2024 Mar.
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D348N Mutation of BFSP1 Gene in Congenital Cataract: it Does Matter.BFSP1 基因 D348N 突变与先天性白内障:有关系。
Cell Biochem Biophys. 2023 Dec;81(4):757-763. doi: 10.1007/s12013-023-01169-6. Epub 2023 Sep 4.
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Elevated levels of FMRP-target MAP1B impair human and mouse neuronal development and mouse social behaviors via autophagy pathway.FMRP 靶向蛋白 MAP1B 水平升高通过自噬途径损害人类和小鼠神经元发育及小鼠社交行为。
Nat Commun. 2023 Jun 26;14(1):3801. doi: 10.1038/s41467-023-39337-0.