Nature Structural & Molecular Biology, 4 January, 2024, DOI：https://doi.org/10.1038/s41594-023-01165-7

Aurora kinase A-mediated phosphorylation triggers structural alteration of Rab1A to enhance ER complexity during mitosis

Wei Zhang, Zijian Zhang, Yun Xiang, Dong-Dong Gu, Jinna Chen, Yifan Chen, Shixian Zhai, Yong Liu, Tao Jiang, Chong Liu, Bin He, Min Yan, Zifeng Wang, Jie Xu, Yu-Lu Cao, Bing Deng, Deshun Zeng, Jie Lei, Junxiao Zhuo, Xinxing Lei, Zijie Long, Bilian Jin, Tongsheng Chen, Dong Li, Yidong Shen, Junjie Hu, Song Gao & Quentin Liu

Abstract

Morphological rearrangement of the endoplasmic reticulum (ER) is critical for metazoan mitosis. Yet, how the ER is remodeled by the mitotic signaling remains unclear. Here, we report that mitotic Aurora kinase A (AURKA) employs a small GTPase, Rab1A, to direct ER remodeling. During mitosis, AURKA phosphorylates Rab1A at Thr75. Structural analysis demonstrates that Thr75 phosphorylation renders Rab1A in a constantly active state by preventing interaction with GDP-dissociation inhibitor (GDI). Activated Rab1A is retained on the ER and induces the oligomerization of ER-shaping protein RTNs and REEPs, eventually triggering an increase of ER complexity. In various models, from Caenorhabditis elegans and Drosophila to mammals, inhibition of Rab1A^Thr75 phosphorylation by genetic modifications disrupts ER remodeling. Thus, our study reveals an evolutionarily conserved mechanism explaining how mitotic kinase controls ER remodeling and uncovers a critical function of Rab GTPases in metaphase.

Article link：https://www.nature.com/articles/s41594-023-01165-7