Mutation of the SUMOylation site of Aurora-B disrupts spindle formation and chromosome alignment in oocytes

Shan-Shan Chen; Li Li; Bo Yao; Jia-Lun Guo; Ping-Shuang Lu; Hao-Lin Zhang; Kun-Huan Zhang; Yuan-Jing Zou; Nan-Jian Luo; Shao-Chen Sun; Lin-Lin Hu; Yan-Ping Ren

doi:10.1038/s41420-024-02217-7

Mutation of the SUMOylation site of Aurora-B disrupts spindle formation and chromosome alignment in oocytes

Cell Death Discov. 2024 Oct 22;10(1):447. doi: 10.1038/s41420-024-02217-7.

Authors

Shan-Shan Chen^{1

2

3}, Li Li¹, Bo Yao¹, Jia-Lun Guo¹, Ping-Shuang Lu², Hao-Lin Zhang², Kun-Huan Zhang², Yuan-Jing Zou², Nan-Jian Luo¹, Shao-Chen Sun², Lin-Lin Hu⁴, Yan-Ping Ren⁵

Affiliations

¹ Department of Histology and Embryology, School of Preclinical Medicine, Zunyi Medical University, Zunyi, Guizhou, 563000, China.
² College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China.
³ Department of Reproduction, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215000, China.
⁴ Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China. [email protected].
⁵ Department of Histology and Embryology, School of Preclinical Medicine, Zunyi Medical University, Zunyi, Guizhou, 563000, China. [email protected].

Abstract

Aurora-B is a kinase that regulates spindle assembly and kinetochore-microtubule (KT-MT) attachment during mitosis and meiosis. SUMOylation is involved in the oocyte meiosis regulation through promoting spindle assembly and chromosome segregation, but its substrates to support this function is still unknown. It is reported that Aurora-B is SUMOylated in somatic cells, and SUMOylated Aurora-B contributes the process of mitosis. However, whether Aurora-B is SUMOylated in oocytes and how SUMOylation of Aurora-B impacts its function in oocyte meiosis remain poorly understood. In this study, we report that Aurora-B is modified by SUMOylation in mouse oocytes. The results show that Aurora-B colocalized and interacted with SUMO-2/3 in mouse oocytes, confirming that Aurora-B is modified by SUMO-2/3 in this system. Compared with that in young mice, the protein expression of SUMO-2/3 decreased in the oocytes of aged mice, indicating that SUMOylation might be related to mouse aging. Overexpression of Aurora-B SUMOylation site mutants, Aurora-B^K207R and Aurora-B^K292R, inhibited Aurora-B recruitment and first polar body extrusion, disrupting localization of gamma tubulin, spindle formation and chromosome alignment in oocytes. The results show that it was related to decreased recruitment of p-HDAC6 which induces the high stability of whole spindle microtubules including the microtubules of both correct and wrong KT-MT attachments though increased acetylation of microtubules. Therefore, our results corroborate the notion that Aurora-B activity is regulated by SUMO-2/3 in oocytes, and that SUMOylated Aurora B plays an important role in spindle formation and chromosome alignment.