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 t...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.展开更多
文摘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.
