STYXL1 regulates CCT complex assembly and flagellar tubulin folding in sperm formation

Yu Chen, Mengjiao Luo, Haixia Tu, Yaling Qi, Yueshuai Guo, Xiangzheng Zhang, Yiqiang Cui, Mengmeng Gao, Xin Zhou, Tianyu Zhu, Hui Zhu, Chenghao Situ (), Yan Li () and Xuejiang Guo ()
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Yu Chen: Nanjing Medical University
Mengjiao Luo: Nanjing Medical University
Haixia Tu: Nanjing Medical University
Yaling Qi: Nanjing Medical University
Yueshuai Guo: Nanjing Medical University
Xiangzheng Zhang: Nanjing Medical University
Yiqiang Cui: Nanjing Medical University
Mengmeng Gao: Nanjing Medical University
Xin Zhou: Nanjing Medical University
Tianyu Zhu: Nanjing Medical University
Hui Zhu: Nanjing Medical University
Chenghao Situ: Nanjing Medical University
Yan Li: Sir Run Run Hospital, Nanjing Medical University
Xuejiang Guo: Nanjing Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Tubulin-based microtubule is a core component of flagella axoneme and essential for sperm motility and male fertility. Structural components of the axoneme have been well explored. However, how tubulin folding is regulated in sperm flagella formation is still largely unknown. Here, we report a germ cell-specific co-factor of CCT complex, STYXL1. Deletion of Styxl1 results in male infertility and microtubule defects of sperm flagella. Proteomic analysis of Styxl1-/- sperm reveals abnormal downregulation of flagella-related proteins including tubulins. The N-terminal rhodanese-like domain of STYXL1 is important for its interactions with CCT complex subunits, CCT1, CCT6 and CCT7. Styxl1 deletion leads to defects in CCT complex assembly and tubulin polymerization. Collectively, our findings reveal the vital roles of germ cell-specific STYXL1 in CCT-facilitated tubulin folding and sperm flagella development.

Date: 2024
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DOI: 10.1038/s41467-023-44337-1

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