Mps1 dimerization and multisite interactions with Ndc80 complex enable responsive spindle assembly checkpoint signaling

• 作者: Divine M.Sedzro Dongmei Wang Fangwei Wang Felix O.Aikhionbare Mohan Hei Najdat Zohbi Ping Gui Sikai Liu Wei Tian Xiao Yuan Xinjiao Gao Xuebiao Yao Yihan Yao Zhen Dou
• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2020,（7）
• 所属期刊栏目: Articles
• 页码范围: 486-498
• 页数: 13页
• 语种: 英文
• DOI: 10.1093/jmcb/mjaa006

摘要

Error-free mitosis depends on accurate chromosome attachment to spindle microtubules,which is monitored by the spindle assembly checkpoint (SAC) signaling.As an upstream factor of SAC,the precise and dynamic kinetochore localization of Mps1 kinase is critical for initiating and silencing SAC signaling.However,the underlying molecular mechanism remains elusive.Here,we demonstrated that the multisite interactions between Mps1 and Ndc80 complex (Ndc80C) govern Mps1 kinetochore targeting.Importantly,we identified direct interaction between Mps1 tetratricopeptide repeat domain and Ndc80C.We further identified that Mps1 C-terminal fragment,which contains the protein kinase domain and C-tail,enhances Mps1 kinetochore localization.Mechanistically,Mps1 C-terminal fragment mediates its dimerization.Perturbation of C-tail attenuates the kinetochore targeting and activity of Mps1,leading to aberrant mitosis due to compromised SAC function.Taken together,our study highlights the importance of Mps1 dimerization and multisite interactions with Ndc80C in enabling responsive SAC signaling.