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Updated: Jun 4, 2025
Meiotic Spindle Assessment in Mouse Oocytes by siRNA-mediated Silencing
Published on: October 11, 2015
A Microtubule-Associated Protein Functions in Preventing Oocytes from Evading the Spindle Assembly Checkpoint
Changyin Zhou1,2, Xue Zhang1, Genlu Xu1,2
1Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China.
Abstract:
Aneuploidy eggs are a common cause of human infertility, spontaneous abortion, or trisomy syndromes. The spindle assembly checkpoint (SAC) plays a crucial role in preventing aneuploidy in oocytes, yet it is unclear if additional mechanisms exist to ensure oocyte adherence to this checkpoint. It is now revealed that the microtubule-associated protein NUSAP can prevent oocytes from evading the SAC and regulate the speed of the cell cycle. Mechanistically, the study identifies NUSAP as a novel stabilizer of the E3 ubiquitin ligase APC/CCDH1, protecting CDH1 from SCFBTRC-mediated degradation. Depletion of NUSAP reduces CDH1 protein level, leading to abnormal spindle assembly and chromosome alignment, and disrupting the balance of cell cycle proteins. This misregulated balance causes oocytes to evade the SAC. Consequently, these abnormal oocytes not only fail to arrest at metaphase but also accelerate the cell process, ultimately resulting in the production of aneuploid eggs. Together, the findings not only clarify the existence of mechanisms that ensure oocytes compliance with the spindle assembly checkpoint but also expand the new functions of NUSAP beyond its role as a microtubule- associated protein.
Insights
The microtubule-associated protein NUSAP prevents aneuploid eggs by stabilizing a key cell cycle protein, ensuring proper chromosome alignment and cell cycle regulation in oocytes.
Area of Science:
- Cell Biology
- Reproductive Biology
- Genetics
Background:
- Aneuploidy in eggs contributes to infertility and developmental disorders.
- The spindle assembly checkpoint (SAC) is vital for preventing aneuploidy.
- Existing mechanisms ensuring oocyte SAC adherence require further elucidation.
Purpose of the Study:
- To investigate novel mechanisms ensuring oocyte compliance with the spindle assembly checkpoint.
- To identify the role of the microtubule-associated protein NUSAP in oocyte SAC regulation.
Main Methods:
- Investigated NUSAP's interaction with the E3 ubiquitin ligase APC/CCDH1.
- Assessed the impact of NUSAP depletion on CDH1 protein levels and stability.
- Analyzed spindle assembly, chromosome alignment, and cell cycle progression in oocytes.
Main Results:
- NUSAP stabilizes APC/CCDH1, preventing its degradation.
- NUSAP depletion leads to reduced CDH1 levels, causing SAC evasion.
- Abnormal spindle assembly, chromosome misalignment, and accelerated cell cycles result in aneuploid eggs.
Conclusions:
- NUSAP plays a critical role in maintaining oocyte SAC fidelity.
- NUSAP functions as a novel stabilizer of APC/CCDH1, extending its known functions.
- Understanding NUSAP's role offers insights into preventing aneuploidy and infertility.
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