CCDC38 is required for sperm flagellum biogenesis and male fertility in mice
CCDC38 is required for sperm flagellum biogenesis and male fertility in mice
复制标题
CCDC38 是小鼠精子鞭毛生物发生和雄性生育能力所必需的
作者：
Ruidan Zhang;Bingbing Wu;Chao Liu;Zhe Zhang;Xiuge Wang;Liying Wang;Sai Xiao;Yinghong Chen;Huafang Wei;Hui Jiang;Fei Gao;Li Yuan;Wei Li
摘要精子鞭毛是男性生育所必需的，鞭毛生物发生缺陷与男性不育有关。螺旋线圈结构域(CCDC)42(CCDC42)缺失与小鼠精子鞭毛的畸形有关。在这里，我们发现睾丸特异蛋白CCDC38与CCDC42相互作用，定位于精子发生过程中的套架和精子尾部。CCDC38在雄性小鼠体内失活会导致套索扭曲，精子鞭毛出现多种形态异常，最终导致男性不育。此外，我们发现CCDC38与鞭毛内运输蛋白88(IFT88)和外周致密纤维蛋白2(ODF2)相互作用，CCDC38的敲除减少了ODF2到鞭毛的运输。总之，我们的结果揭示了CCDC38在精子鞭毛生物发生中的重要作用，并提示这些基因的一些突变可能与人类男性不育有关。
ABSTRACT The sperm flagellum is essential for male fertility, and defects in flagellum biogenesis are associated with male infertility. Deficiency of coiled-coil domain-containing (CCDC) 42 (CCDC42) is specifically associated with malformation of mouse sperm flagella. Here, we find that the testis-specific protein CCDC38 interacts with CCDC42, localizing on the manchette and sperm tail during spermiogenesis. Inactivation of CCDC38 in male mice results in a distorted manchette, multiple morphological abnormalities of the flagella of spermatozoa and eventually male sterility. Furthermore, we find that CCDC38 interacts with intraflagellar transport protein 88 (IFT88), as well as outer dense fibrous 2 (ODF2), and the knockout of Ccdc38 reduces transport of ODF2 to the flagellum. Altogether, our results uncover the essential role of CCDC38 in sperm flagellum biogenesis, and suggest that some mutations of these genes might be associated with male infertility in humans.