Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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.

PubMed Disclaimer

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

References

    1. Nogales E, Wang H Structural intermediates in microtubule assembly and disassembly: how and why? Curr Opin Cell Biol. 2006;18(2):179–184. doi: 10.1016/j.ceb.2006.02.009. - DOI - PubMed
    1. Brouhard GJ Dynamic instability 30 years later: complexities in microtubule growth and catastrophe. Mol Biol Cell. 2015;26(7):1207–1210. doi: 10.1091/mbc.E13-10-0594. - DOI - PMC - PubMed
    1. Gardner MK, Zanic M, Howard J Microtubule catastrophe and rescue. Curr Opin Cell Biol. 2013;25(1):14–22. doi: 10.1016/j.ceb.2012.09.006. - DOI - PMC - PubMed
    1. Walczak CE, Heald R Mechanisms of mitotic spindle assembly and function. https://www.sciencedirect.com/science/article/abs/pii/S0074769607650037. Int Rev Cytol. 2008;265:111–158. - PubMed
    1. Errico A, Ballabio A, Rugarli EI Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics. Hum Mol Genet. 2002;11(2):153–163. doi: 10.1093/hmg/11.2.153. - DOI - PubMed

LinkOut - more resources