Aurora A orchestrates entosis by regulating a dynamic MCAK-TIP150 interaction.
Entosis, a cell-in-cell process, has been implicated in the formation of aneuploidy associated with an aberrant cell division control. Microtubule plus-end-tracking protein TIP150 facilitates the loading of MCAK onto the microtubule plus ends and orchestrates microtubule plus-end dynamics during cell division. Here we show that TIP150 cooperates with MCAK to govern entosis via a regulatory circuitry that involves Aurora A-mediated phosphorylation of MCAK. Our biochemical analyses show that MCAK forms an intra-molecular association, which is essential for TIP150 binding. Interestingly, Aurora A-mediated phosphorylation of MCAK modulates its intra-molecular association, which perturbs the MCAK-TIP150 interaction in vitro and inhibits entosis in vivo. To probe if MCAK-TIP150 interaction regulates microtubule plasticity to affect the mechanical properties of cells during entosis, we used an optical trap to measure the mechanical rigidity of live MCF7 cells. We find that the MCAK cooperates with TIP150 to promote microtubule dynamics and modulate the mechanical rigidity of the cells during entosis. Our results show that a dynamic interaction of MCAK-TIP150 orchestrated by Aurora A-mediated phosphorylation governs entosis via regulating microtubule plus-end dynamics and cell rigidity. These data reveal a previously unknown mechanism of Aurora A regulation in the control of microtubule plasticity during cell-in-cell processes.
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China.
Peng
P
Xia
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China.
Jinhua
J
Zhou
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China.
Xiaoyu
X
Song
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China.
Bing
B
Wu
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China Molecular Imaging Center, Atlanta Clinical and Translational Science Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Xing
X
Liu
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China.
Di
D
Li
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China.
Shuyuan
S
Zhang
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China Molecular Imaging Center, Atlanta Clinical and Translational Science Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Zhikai
Z
Wang
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China.
Huijuan
H
Yu
Molecular Imaging Center, Atlanta Clinical and Translational Science Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA Harvard Medical School, Boston, MA 02115, USA.
Tarsha
T
Ward
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China Guangzhou Institutes of Biomedicine and Health, Guangzhou 510513, China.
Jiancun
J
Zhang
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China.
Yinmei
Y
Li
The 301 Hospital, Beijing 100039, China.
Xiaoning
X
Wang
Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Yong
Y
Chen
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China Molecular Imaging Center, Atlanta Clinical and Translational Science Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA yaoxb@ustc.edu.cn zhenguo@ustc.edu.cn.
Zhen
Z
Guo
Anhui Key Laboratory of Cellular Dynamics & Chemical Biology, Department of Optics and Optical Engineering, and Hefei National Laboratory for Physical Sciences at Nanoscale, University of Science and Technology of China, Hefei 230027, China yaoxb@ustc.edu.cn zhenguo@ustc.edu.cn.
Xuebiao
X
Yao
D064096:Aurora Kinase A / Q000378:metabolism*; D057691:Entosis; D057809:HEK293 Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D061986:MCF-7 Cells; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation; D058105:Polymerization; D011485:Protein Binding
C091489:KIF2C protein, human; C546899:MTUS2 protein, human; D008869:Microtubule-Associated Proteins; D050505:Mutant Proteins; C576917:AURKA protein, human; D064096:Aurora Kinase A; D016547:Kinesins
Aurora A; MCAK; TIP150; entosis; kinesin; microtubule plus-end