Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030.
Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871, Japan.
Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5370-E5378. doi: 10.1073/pnas.1621279114. Epub 2017 Jun 19.
Flagella and cilia are critical cellular organelles that provide a means for cells to sense and progress through their environment. The central component of flagella and cilia is the axoneme, which comprises the "9+2" microtubule arrangement, dynein arms, radial spokes, and the nexin-dynein regulatory complex (-DRC). Failure to properly assemble components of the axoneme leads to defective flagella and in humans leads to a collection of diseases referred to as ciliopathies. Ciliopathies can manifest as severe syndromic diseases that affect lung and kidney function, central nervous system development, bone formation, visceral organ organization, and reproduction. T-Complex-Associated-Testis-Expressed 1 (TCTE1) is an evolutionarily conserved axonemal protein present from (DRC5) to mammals that localizes to the -DRC. Here, we show that mouse TCTE1 is testis-enriched in its expression, with its mRNA appearing in early round spermatids and protein localized to the flagellum. TCTE1 is 498 aa in length with a leucine rich repeat domain at the C terminus and is present in eukaryotes containing a flagellum. Knockout of results in male sterility because -null spermatozoa show aberrant motility. Although the axoneme is structurally normal in mutant spermatozoa, -null sperm demonstrate a significant decrease of ATP, which is used by dynein motors to generate the bending force of the flagellum. These data provide a link to defining the molecular intricacies required for axoneme function, sperm motility, and male fertility.
鞭毛和纤毛是细胞感知和在环境中移动的关键细胞器。鞭毛和纤毛的核心组件是轴丝，它由“9+2”微管排列、动力蛋白臂、辐条和中心体-动力蛋白调节复合物（-DRC）组成。轴丝组件组装不当会导致鞭毛缺陷，在人类中会导致一系列称为纤毛病的疾病。纤毛病可以表现为严重的综合征疾病，影响肺和肾功能、中枢神经系统发育、骨骼形成、内脏器官组织和生殖。T 复合体相关睾丸表达蛋白 1（TCTE1）是一种进化上保守的轴丝蛋白，存在于从（DRC5）到哺乳动物的轴丝中，定位于-DRC。在这里，我们表明，小鼠 TCTE1 在其表达中睾丸丰富，其 mRNA 出现在早期圆形精子细胞中，蛋白定位于鞭毛。TCTE1 长 498 个氨基酸，C 末端有一个富含亮氨酸的重复结构域，存在于含有鞭毛的真核生物中。敲除导致雄性不育，因为 -null 精子表现出异常的运动能力。尽管在 -null 精子的轴丝结构正常，但 -null 精子的 ATP 显著减少，而 ATP 是动力蛋白马达产生鞭毛弯曲力所必需的。这些数据为定义轴丝功能、精子运动和男性生育力所需的分子复杂性提供了联系。
