A research team led by Prof. YAO Xuebiao, LIU Xing and ZANG Jianye from University of Science and Technology of China (USTC) revealed how crotonylation of EB1 helped orientate spindle in mitosis. The study was published in Nature Chemical Biology, and a review of this study was also published in Nature Chemical Biology.

Spindle, located in the nucleus, is an essential membraneless organelle that promises the equal allocation of chromosome during mitosis. Spindle position control is of significant importance for cell fate determination and organogenesis. And the disturbance of spindle could lead to canceration of cell.

TIP60 is an important acetyltransferase that regulates the genomic stability of eukaryotic cells. Mutations in TIP60 signal axis gene increase susceptibility to gastric cancer.  

The researchers in this work identified EB1, a core and scaffold microtubule plus-end tracking protein, as a substrate of TIP60. In mitotic cells, EB1 is drastically crotonylated at Lys66 and forms a binding protein with TIP60. Using unnatural amino acids incorporation method, they found that the binding protein helps spindle positioning by manipulating the plasticity of astral microtubules.

In order to simulate the intervention effect of Helicobacter pylori mediating abnormal EB1 bastilylation on gastric epithelial cell renewal quality, the researchers conducted a series of experiments on mice to mimic parophysiological state. They generated visible three-dimension gastric organoids by knocking in TIP60 in mice. Through total internal reflection fluorescence microscopy, they systematically evaluated the physiological function of TIP60-EB1 crobitoylation and elucidated the quality control mechanism of gastric epithelial cell renewal.

The study revealed how EB1 crotonylation by TIP60 ensured the accuracy of spindle positioning which may contribute to a more explicit understanding of mitosis. It also provides a unique targeted chemical biological technique strategy for dynamic intervention in helicobacter pylori mediated inflammatory-cancer transformation.

Paper link: https://www.nature.com/articles/s41589-021-00875-7 

（Written by MIAO Xinyi, edted by LU Hongyu, USTC News Center)