Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice.,PLOS Genetics

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Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice.
PLOS Genetics ( IF 4.0 ) Pub Date : 2020-01-21 , DOI: 10.1371/journal.pgen.1008585
Akane Morohoshi _{1,

2} , Haruhiko Miyata ₁ , Keisuke Shimada ₁ , Kaori Nozawa ₁ , Takafumi Matsumura _{1,

3} , Ryuji Yanase ₄ , Kogiku Shiba ₄ , Kazuo Inaba ₄ , Masahito Ikawa _{1,

2,

3,

5}

Affiliation

Flagella and cilia are evolutionarily conserved cellular organelles. Abnormal formation or motility of these organelles in humans causes several syndromic diseases termed ciliopathies. The central component of flagella and cilia is the axoneme that is composed of the '9+2' microtubule arrangement, dynein arms, radial spokes, and the Nexin-Dynein Regulatory Complex (N-DRC). The N-DRC is localized between doublet microtubules and has been extensively studied in the unicellular flagellate Chlamydomonas. Recently, it has been reported that TCTE1 (DRC5), a component of the N-DRC, is essential for proper sperm motility and male fertility in mice. Further, TCTE1 has been shown to interact with FBXL13 (DRC6) and DRC7; however, functional roles of FBXL13 and DRC7 in mammals have not been elucidated. Here we show that Fbxl13 and Drc7 expression are testes-enriched in mice. Although Fbxl13 knockout (KO) mice did not show any obvious phenotypes, Drc7 KO male mice were infertile due to their short immotile spermatozoa. In Drc7 KO spermatids, the axoneme is disorganized and the '9+2' microtubule arrangement was difficult to detect. Further, other N-DRC components fail to incorporate into the flagellum without DRC7. These results indicate that Drc7, but not Fbxl13, is essential for the correct assembly of the N-DRC and flagella.

中文翻译：

Nexin-Dynein调节复合物成分DRC7但不是FBXL13是小鼠精子鞭毛形成和雄性育性所必需的。

鞭毛和纤毛是进化上保守的细胞器。这些细胞器在人体内的异常形成或运动会引起几种症状，称为纤毛病。鞭毛和纤毛的主要成分是轴突，由“ 9 + 2”微管排列，达因臂，radial状辐条和Nexin-Dynein调节复合物（N-DRC）组成。N-DRC位于双峰微管之间，并已在单细胞鞭毛衣藻中进行了广泛研究。最近，据报道，TC-TE1（DRC5）是N-DRC的组成部分，对于小鼠的适当精子运动和雄性育性至关重要。此外，已显示TCTE1与FBXL13（DRC6）和DRC7进行交互。但是，尚未阐明FBXL13和DRC7在哺乳动物中的功能作用。在这里，我们显示Fbxl13和Drc7表达在小鼠体内富含睾丸。尽管Fbxl13基因敲除（KO）小鼠没有表现出任何明显的表型，但Drc7 KO雄性小鼠由于不能活动的精子短而不能育。在Drc7 KO精子中，轴突杂乱无章，很难检测到“ 9 + 2”微管排列。此外，如果没有DRC7，其他N-DRC组件也无法合并到鞭毛中。这些结果表明，Drc7，而不是Fbxl13，对于正确组装N-DRC和鞭毛至关重要。没有DRC7，其他N-DRC组件就无法合并到鞭毛中。这些结果表明，Drc7，而不是Fbxl13，对于正确组装N-DRC和鞭毛至关重要。没有DRC7，其他N-DRC组件就无法合并到鞭毛中。这些结果表明，Drc7，而不是Fbxl13，对于正确组装N-DRC和鞭毛至关重要。

更新日期：2020-02-18

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