Aurora A orchestrates entosis by regulating a dynamic MCAK-TIP150 interaction  

作　　者：PengXia JinhuaZhou Xiaoyu Song BingWu XingLiu Di Li Shuyuan Zhang Zhikai Wang H uijuan Yu Tarsha Ward Jiancun Zhang Yinmei Li Xiaoning Wang YongChen Zhen Guo Xuebiao Yao 

机构地区：[1]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 [2]Molecular Imaging Center, Atlanta Clinical and Translational Science Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA [3]Harvard Medical School, Boston, MA 02115, USA [4]Guangzhou Institutes of Biomedicine and Health, Guangzhou 510513, China [5]The 301 Hospital, Beijing 100039, China [6]Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China

出　　处：《Journal of Molecular Cell Biology》2014年第3期240-254,共15页分子细胞生物学报（英文版）

摘　　要：Entosis, a ceU-in-ceU process, has been implicated in the formation of aneuploidy associated with an aberrant cell division control. Microtubule plus-end-tracking protein TI P150 facilitates the loading of MCAK onto the microtubule plus ends and orchestrates micro- tubule plus-end dynamics during cell division. Here we show that TIP150 cooperates with MCAK to govern entosis via a regulatory cir- cuitry 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-mo- lecular association, which perturbs the MCAK-TI P150 interaction in vitro and inhibits entosis in vivo. To probe if MCAK-TIP150 inter- action regulates microtubule plasticity to affect the mechanical properties of ceUs during entosis, we used an optical trap to measure the mechanical rigidity of live MCF7 ceils. 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-TI P150 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 ceU-in-ceU pro- cesses.

关 键 词：Aurora A TIP150 MCAK entosis microtubule plus-end KINESIN 

分 类 号：Q51[生物学—生物化学] S865.13[农业科学—野生动物驯养]