Dynamic organelle distribution initiates actin-based spindle migration in mouse oocytes

Xing Duan, Yizeng Li, Kexi Yi, Fengli Guo, Hai Yang Wang, Pei Hsun Wu, Jing Yang, Devin B. Mair, Edwin Angelo Morales, Petr Kalab, Denis Wirtz, Sean X. Sun, Rong Li

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Abstract

Migration of meiosis-I (MI) spindle from the cell center to a sub-cortical location is a critical step for mouse oocytes to undergo asymmetric meiotic cell division. In this study, we investigate the mechanism by which formin-2 (FMN2) orchestrates the initial movement of MI spindle. By defining protein domains responsible for targeting FMN2, we show that spindle-periphery localized FMN2 is required for spindle migration. The spindle-peripheral FMN2 nucleates short actin bundles from vesicles derived likely from the endoplasmic reticulum (ER) and concentrated in a layer outside the spindle. This layer is in turn surrounded by mitochondria. A model based on polymerizing actin filaments pushing against mitochondria, thus generating a counter force on the spindle, demonstrated an inherent ability of this system to break symmetry and evolve directional spindle motion. The model is further supported through experiments involving spatially biasing actin nucleation via optogenetics and disruption of mitochondrial distribution and dynamics.

Original languageEnglish (US)
Article number277
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Duan, X., Li, Y., Yi, K., Guo, F., Wang, H. Y., Wu, P. H., Yang, J., Mair, D. B., Morales, E. A., Kalab, P., Wirtz, D., Sun, S. X., & Li, R. (2020). Dynamic organelle distribution initiates actin-based spindle migration in mouse oocytes. Nature communications, 11(1), [277]. https://doi.org/10.1038/s41467-019-14068-3