Soto-Moreno Edgar J, Ali Nourhan N, Küllmer Florian, Nasufovic Veselin, Frolikova Michaela, Tepla Olga, Masata Jaromir, Trauner Dirk, Patterson Amanda A, Arndt Hans-Dieter, Komrskova Katerina, Zernicka-Goetz Magdalena, Glover David M, Balboula Ahmed Z
Division of Animal Sciences, University of Missouri, Columbia, MO, USA.
Friedrich-Schiller-Universität (FSU), Institut für Organische Chemie und Makromolekulare Chemie, Jena, Germany.
Nat Commun. 2025 Sep 19;16(1):8323. doi: 10.1038/s41467-025-63586-w.
Mammalian oocytes are notoriously prone to chromosome segregation errors leading to aneuploidy. The spindle provides the machinery for accurate chromosome segregation during cell division. Mammalian oocytes lack centrioles and, therefore, mouse meiotic spindle relies on the organization of numerous acentriolar microtubule organizing centers into two poles (polar microtubule organizing centers, pMTOCs). The traditional view is that, in mammalian oocytes, microtubules are the sole cytoskeletal component responsible for regulating pMTOC organization and spindle assembly. We identify a previously unrecognized F-actin pool that surrounds pMTOCs, forming F-actin cage-like structure. We demonstrate that F-actin localization on the spindle depends on unconventional myosins X and VIIb. Selective disruption of spindle-localized F-actin, using myosin X/VIIb knockdown oocytes or photoswitchable Optojasp-1, perturbs pMTOC organization, leading to unfocused spindle poles and chromosome missegregation. Here, we unveil an important function of spindle-localized F-actin in regulating pMTOC organization, a critical process for ensuring the fidelity of meiotic spindle formation and proper chromosome segregation.
哺乳动物的卵母细胞极易出现导致非整倍体的染色体分离错误。纺锤体为细胞分裂过程中染色体的精确分离提供机制。哺乳动物的卵母细胞缺乏中心粒，因此，小鼠减数分裂纺锤体依赖于众多无中心粒微管组织中心排列成两极（极微管组织中心，pMTOC）。传统观点认为，在哺乳动物卵母细胞中，微管是负责调节pMTOC组织和纺锤体组装的唯一细胞骨架成分。我们发现了一个先前未被识别的围绕pMTOC的F-肌动蛋白池，形成F-肌动蛋白笼状结构。我们证明，纺锤体上F-肌动蛋白的定位取决于非常规肌球蛋白X和VIIb。使用肌球蛋白X/VIIb敲低的卵母细胞或光开关Optojasp-1选择性破坏纺锤体定位的F-肌动蛋白，会扰乱pMTOC组织，导致纺锤体极不聚焦和染色体错误分离。在这里，我们揭示了纺锤体定位的F-肌动蛋白在调节pMTOC组织中的重要功能，这是确保减数分裂纺锤体形成的保真度和正确染色体分离的关键过程。
