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. 2024 May 29;38(5):485-499.
doi: 10.7555/JBR.37.20230290.

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

Shiya Xie  1   2   3 , Yanjie Yang  1   2   3 , Zhen Jin  4   5 , Xiaocong Liu  6 , Shuping Zhang  1 , Ning Su  1 , Jiaqi Liu  1 , Congrong Li  1 , Dong Zhang  1   3 , Leilei Gao  4 , Zhixia Yang  2
Affiliations

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

Shiya Xie et al. J Biomed Res. .

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: KL2; MTSE; female meiosis; kinase; mouse.

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Conflict of interest statement

The authors reported no conflict of interests.

Figures

Figure 1
Figure 1
Mouse katanin-like 2 (KL2) was a unique microtubule severing enzyme (MTSE) associated with chromosome-based spindle organization in mouse oocytes.
Figure 2
Figure 2
KL2 was important for normal meiosis progression and fertility in mouse oocytes.
Figure 3
Figure 3
Aurora B was indispensable for KL2 localization to the chromosome in mouse oocytes.
Figure 4
Figure 4
KL2 localization to the chromosomes was modulated by phosphorylated eukaryotic elongation factor-2 kinase (p-eEF2K) in mouse oocytes.
Figure 5
Figure 5
ERK 1/2 regulated the relocation of KL2 to spindle poles via phosphorylation at Tyr5 (Y5) and Thr7 (T7) in mouse oocytes.
Figure 6
Figure 6
Aurora B, p-eEF2K, and ERK 1/2 coordinate to modulate the chromosomal localization of KL2 in a "multilevel focus-adjusting" manner in mouse oocytes.
See this image and copyright information in PMC

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