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Updated: Jun 25, 2025
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Published on: October 11, 2022
Mouse KL2 is a unique MTSE involved in chromosome-based spindle organization and regulated by multiple kinases during
Shi-Ya Xie1,2,3, Yan-Jie Yang1,2,3, Zhen Jin4,5
1State Key Lab of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Abstract:
Microtubule-severing enzymes (MTSEs) play important roles in mitosis and meiosis of the primitive organisms. However, their roles in mammalian female meiosis, which accounts for over 80% of gamete-originated human reproductive diseases, remain unexplored. In the current study, we reported that katanin-like 2 (KL2) was the only MTSE concentrating at chromosomes. Furthermore, the knockdown of KL2 significantly reduced the chromosome-based increase in the microtubule (MT) polymer, increased aberrant kinetochore-MT (K-MT) attachment, delayed meiosis, and severely affected normal fertility. We demonstrated that the inhibition of aurora B, a key kinase for correcting aberrant K-MT attachment, significantly eliminated KL2 expression from chromosomes. Additionally, KL2 interacted with phosphorylated eukaryotic elongation factor-2 kinase, and they competed for chromosome binding. Phosphorylated KL2 was also localized at spindle poles, with its phosphorylation regulated by extracellular signal-regulated kinase 1/2. In summary, the current study reveals a novel function of MTSEs in mammalian female meiosis and demonstrates that multiple kinases coordinate to regulate the levels of KL2 at chromosomes.
Insights
Katanin-like 2 (KL2), a microtubule-severing enzyme, is crucial for mammalian female meiosis, ensuring proper chromosome attachment and fertility. Its regulation by kinases prevents reproductive diseases.
Area of Science:
- Cell Biology
- Reproductive Biology
- Molecular Biology
Background:
- Microtubule-severing enzymes (MTSEs) are vital in primitive organism meiosis.
- Mammalian female meiosis abnormalities cause over 80% of human reproductive diseases.
- The role of MTSEs in mammalian female meiosis remains unexplored.
Purpose of the Study:
- Investigate the function of MTSEs in mammalian female meiosis.
- Identify specific MTSEs involved in chromosome regulation.
- Elucidate the regulatory mechanisms of MTSEs during meiosis.
Main Methods:
- Identified katanin-like 2 (KL2) as the sole MTSE at chromosomes.
- Utilized KL2 knockdown to assess its meiotic functions.
- Investigated KL2 interactions with kinases like aurora B and eEF2K.
- Analyzed KL2 phosphorylation by ERK1/2.
Main Results:
- KL2 knockdown impaired microtubule polymerization, increased aberrant kinetochore-MT attachment, and delayed meiosis.
- KL2 localization to chromosomes depends on aurora B activity.
- KL2 competes with phosphorylated eEF2K for chromosome binding.
- KL2 phosphorylation, regulated by ERK1/2, influences its spindle pole localization.
Conclusions:
- KL2 plays a novel, essential role in mammalian female meiosis.
- Aberrant kinetochore-MT attachment and fertility are linked to KL2 function.
- Kinase networks involving aurora B, eEF2K, and ERK1/2 precisely regulate KL2 localization and function during meiosis.
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