Dual control of formin-nucleated actin assembly by the chromatin and ER in mouse oocytes

Hai Yang Wang, Jinrong Hu, Kexi Yi, Zhiming Ma, Xin Jie Song, Yaelim Lee, Petr Kalab, Alexander D. Bershadsky, Yansong Miao, Rong Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

The first asymmetric meiotic cell divisions in mouse oocytes are driven by formin 2 (FMN2)-nucleated actin polymerization around the spindle. In this study, we investigated how FMN2 is recruited to the spindle peripheral ER and how its activity is regulated in mouse meiosis I (MI) oocytes. We show that this process is regulated by the Ran GTPase, a conserved mediator of chromatin signal, and the ER-associated protein VAPA. FMN2 contains a nuclear localization sequence (NLS) within a domain (SLD) previously shown to be required for FMN2 localization to the spindle periphery. FMN2 NLS is bound to the importin α1/β complex, and the disruption of this interaction by RanGTP is required for FMN2 accumulation in the area proximal to the chromatin and the MI spindle. The importin-free FMN2 is then recruited to the surface of ER around the spindle through the binding of the SLD with the ER-membrane protein VAPA. We further show that FMN2 is autoinhibited through an intramolecular interaction between the SLD with the C-terminal formin homology 2 (FH2) domain that nucleates actin filaments. VAPA binding to SLD relieves the autoinhibition of FMN2, leading to localized actin polymerization. This dual control of formin-mediated actin assembly allows actin polymerization to initiate the movement of the meiotic spindle toward the cortex, an essential step in the maturation of the mammalian female gamete.

Original languageEnglish
Pages (from-to)4013-4024.e6
JournalCurrent Biology
Volume32
Issue number18
DOIs
Publication statusPublished - 26 Sept 2022

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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