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Mouse KL2 is a unique MTSE involved in chromosome-based spindle organization and regulated by multiple kinases during female meiosis

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… Click to show full 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.

Keywords: multiple kinases; meiosis; female meiosis; kl2; chromosome based

Journal Title: Journal of Biomedical Research
Year Published: 2024

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