STK33 Phosphorylates Fibrous Sheath Protein AKAP3/4 to Regulate Sperm Flagella Assembly in Spermiogenesis

作者：Weiling Yu, Yang Li, Hong Chen, Yiqiang Cui, Chenghao Situ, Liping Yao, Xiangzheng Zhang, Shuai Lü, Li Liu, Laihua Li, Jie Ren, Yueshuai Guo, Zian Huo, Yu Chen, Haojie Li, Tao Jiang, Yayun Gu, Cheng Wang, Tianyu Zhu, Yan Li, Zhibin Hu, Xuejiang Guo · 发表于：Molecular & Cellular Proteomics · 年份：2023 · DOI：10.1016/j.mcpro.2023.100564 · 被引用次数：18 · 研究领域：Sperm and Testicular Function、Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities、Reproductive Biology and Fertility

Spermatogenesis defects are important for male infertility; however, the etiology and pathogenesis are still unknown. Herein, we identified two loss-of-function mutations of STK33 in seven individuals with non-obstructive azoospermia. Further functional studies of these frameshift and nonsense mutations revealed that Stk33 -/KI male mice were sterile, and Stk33 -/KI sperm were abnormal with defects in the mitochondrial sheath, fibrous sheath, outer dense fiber, and axoneme. Stk33 KI/KI male mice were subfertile and had oligoasthenozoospermia. Differential phosphoproteomic analysis and in vitro kinase assay identified novel phosphorylation substrates of STK33, fibrous sheath components A-kinase anchoring protein 3 and A-kinase anchoring protein 4, whose expression levels decreased in testis after deletion of Stk33 . STK33 regulated the phosphorylation of A-kinase anchoring protein 3/4, affected the assembly of fibrous sheath in the sperm, and played an essential role in spermiogenesis and male infertility.