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Spindle-localized F-actin regulates polar MTOC organization and the fidelity of meiotic spindle formation

. 2025 Sep 19 ; 16 (1) : 8323. [epub] 20250919

Language English Country Great Britain, England Media electronic

Document type Journal Article

Grant support
R35 GM142537 NIGMS NIH HHS - United States

Links

PubMed 40973727
PubMed Central PMC12449456
DOI 10.1038/s41467-025-63586-w
PII: 10.1038/s41467-025-63586-w
Knihovny.cz E-resources

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.

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