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

作　　者：Shiya Xie Yanjie Yang Zhen Jin Xiaocong Liu Shuping Zhang Ning Su Jiaqi Liu Congrong Li Dong Zhang Leilei Gao Zhixia Yang 

机构地区：[1]State Key Lab of Reproductive Medicine and Offspring Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China [2]Central Laboratory,the First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China [3]Department of Gynaecology and Obstetrics,the First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China [4]Center for Reproductive Medicine,Department of Gynecology,Zhejiang Provincial People's Hospital(Affiliated People's Hospital),Hangzhou Medical College,Hangzhou,Zhejiang 310014,China [5]Center for Reproductive Medicine,Department of Reproductive Endocrinology,Zhejiang Provincial People's Hospital(Affiliated People's Hospital),Hangzhou Medical College,Hangzhou,Zhejiang 310014,China [6]Laboratory Department of Shihezi People's Hospital,Shihezi,Xinjiang 832099,China

出　　处：《Journal of Biomedical Research》2024年第5期485-499,I0009-I0011,共18页生物医学研究杂志（英文版）

基　　金：supported by the Youth Program of National Natural Science Foundation of China(Grant No.82001539 to Leilei Gao);the Zhejiang Province Health Innovation Talent Project(Grant No.2021RC001 to Zhen Jin);the General Program of the National Natural Science Foundation of China(Grant No.31671561 to Dong Zhang);the Regional Program of National Natural Science Foundation of China(Grant No.82260126 to Xiaocong Liu).

摘　　要：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.

关 键 词：MOUSE KL2 MTSE KINASE female meiosis 

分 类 号：R321.1[医药卫生—人体解剖和组织胚胎学]