Mouse KL2 is a unique MTSE involved in chromosome-based spindle organization and regulated by multiple kinases during female meiosis
Shiya Xie1
Yanjie Yang1
Zhen Jin2
Xiaocong Liu3
Shuping Zhang4
Ning Su4
Jiaqi Liu4
Congrong Li4
Dong Zhang5
Leilei Gao6
Zhixia Yang7
1.State Key Lab of Reproductive Medicine and Offspring Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Central Laboratory,the First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China;Department of Gynaecology and Obstetrics,the First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China2.Center for Reproductive Medicine,Department of Gynecology,Zhejiang Provincial People's Hospital(Affiliated People's Hospital),Hangzhou Medical College,Hangzhou,Zhejiang 310014,China;Center for Reproductive Medicine,Department of Reproductive Endocrinology,Zhejiang Provincial People's Hospital(Affiliated People's Hospital),Hangzhou Medical College,Hangzhou,Zhejiang 310014,China3.Laboratory Department of Shihezi People's Hospital,Shihezi,Xinjiang 832099,China4.State Key Lab of Reproductive Medicine and Offspring Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China5.State Key Lab of Reproductive Medicine and Offspring Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Department of Gynaecology and Obstetrics,the First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China6.Center for Reproductive Medicine,Department of Gynecology,Zhejiang Provincial People's Hospital(Affiliated People's Hospital),Hangzhou Medical College,Hangzhou,Zhejiang 310014,China7.Central Laboratory,the First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China
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.
机标关键词：mousebasedchromosomeduringfemaleinvolvedkinasesmeiosis
分类号：R321.1(人体形态学)
论文发表日期：2024-09-30
在线出版日期：2026-03-31（本平台首次上网日期，不代表文献的发表时间）
页数：16( 中插6,485-499 )
英文信息