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

作　　者：Ping Gui Divine M.Sedzro Xiao Yuan Sikai Liu Mohan Hei Wei Tian Najdat Zohbi Fangwei Wang Yihan Yao Felix O.Aikhionbare Xinjiao Gao Dongmei Wang Xuebiao Yao Zhen Dou 

机构地区：[1]MOE Key Laboratory of Membraneless Organelle and Cellular Dynamics,Hefei National Laboratory for Physical Sciences at the Microscale,School of Life Sciences,University of Science and Technology of China,Hefei 230027,China [2]Keck Center for Cellular Dynamics and Organoids Plasticity,Morehouse School of Medicine,Atlanta,GA 30310,USA [3]Key Laboratory of Molecular Biophysics of the Ministry of Education,College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,China [4]Life Sciences Institute and Innovation Center for Cell Signaling Network,Zhejiang University,Hangzhou 310058,China

出　　处：《Journal of Molecular Cell Biology》2020年第7期486-498,共13页分子细胞生物学报（英文版）

基　　金：supported by the National Key R&D Program of China(2017YFA 0102900 and 2017 YFA 0503600);the National Natural Science Fondation of China(31671407 and 31871359 to Z.D.;31621002,31430054,91854203,and 31320103904 to X.Y.;31301099 and 21672201 to X.G.;31471275 to D.W.),Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19040000);Chinese Academy of Sciences Center for Excellence in Molecular Cell Science(2015 HSC-UE010);MOE Innovative Team(IRT_17R102).

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.

关 键 词：MITOSIS spindle assembly checkpoint KINETOCHORE Mps1 kinase Ndc80 complex 

分 类 号：Q5[生物学—生物化学]