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CENP-F-dependent DRP1 function regulates APC/C activity during oocyte meiosis I
Cheng-Jie Zhou1, Xing-Yue Wang2, Yan-Hua Dong2
1State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, 010070, Hohhot, Inner Mongolia, China. zhoucj@imu.edu.cn.
Nature Communications
|December 13, 2022
Summary
Dynamin-related protein 1 (DRP1) restrains anaphase-promoting complex/cyclosome (APC/C) activity to prevent premature chromosome segregation during meiosis I. DRP1 acts as a spindle assembly checkpoint protein, ensuring proper cell division.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Chromosome segregation relies on cohesin degradation, regulated by the anaphase-promoting complex/cyclosome (APC/C).
- Dynamin-related protein 1 (DRP1), involved in mitochondrial fission, influences cell cycle progression.
- The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation.
Purpose of the Study:
- To investigate the role of Dynamin-related protein 1 (DRP1) in chromosome segregation during mouse oocyte meiosis.
- To elucidate the mechanism by which DRP1 regulates the anaphase-promoting complex/cyclosome (APC/C).
Main Methods:
- Immunoprecipitation to study protein interactions.
- Depletion of DRP1 using acute depletion methods.
- Analysis of cohesin degradation, securin and cyclin B1 levels.
- Microscopy to observe chromosome segregation and kinetochore recruitment.
Main Results:
- DRP1 is recruited to the kinetochore by Centromere protein F (CENP-F) after nuclear envelope breakdown.
- Loss of DRP1 causes premature cohesin degradation and chromosome segregation.
- DRP1 depletion activates separase by initiating cyclin B1 and securin degradation during the metaphase-to-anaphase transition.
- DRP1 binds to APC2, restraining APC/C E3 ligase activity.
Conclusions:
- DRP1 acts as a novel, CENP-F-dependent spindle assembly checkpoint (SAC) protein in meiosis I.
- DRP1 modulates the metaphase-to-anaphase transition by controlling APC/C activity.
- DRP1 plays a critical role in preventing premature chromosome segregation in oocytes.
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