San Agustin Jovenal T, Pazour Gregory J, Witman George B
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
Mol Biol Cell. 2015 Dec 1;26(24):4358-72. doi: 10.1091/mbc.E15-08-0578. Epub 2015 Sep 30.
Drosophila sperm are unusual in that they do not require the intraflagellar transport (IFT) system for assembly of their flagella. In the mouse, the IFT proteins are very abundant in testis, but we here show that mature sperm are completely devoid of them, making the importance of IFT to mammalian sperm development unclear. To address this question, we characterized spermiogenesis and fertility in the Ift88(Tg737Rpw) mouse. This mouse has a hypomorphic mutation in the gene encoding the IFT88 subunit of the IFT particle. This mutation is highly disruptive to ciliary assembly in other organs. Ift88(-/-) mice are completely sterile. They produce ∼ 350-fold fewer sperm than wild-type mice, and the remaining sperm completely lack or have very short flagella. The short flagella rarely have axonemes but assemble ectopic microtubules and outer dense fibers and accumulate improperly assembled fibrous sheath proteins. Thus IFT is essential for the formation but not the maintenance of mammalian sperm flagella.
果蝇精子不同寻常之处在于,它们在鞭毛组装过程中不需要鞭毛内运输(IFT)系统。在小鼠中,IFT蛋白在睾丸中含量非常丰富,但我们在此表明,成熟精子中完全没有这些蛋白,这使得IFT对哺乳动物精子发育的重要性尚不明确。为了解决这个问题,我们对Ift88(Tg737Rpw)小鼠的精子发生和生育能力进行了表征。该小鼠在编码IFT颗粒的IFT88亚基的基因中存在一个亚效突变。这种突变对其他器官的纤毛组装具有高度破坏性。Ift88(-/-)小鼠完全不育。它们产生的精子比野生型小鼠少约350倍,其余精子完全没有鞭毛或鞭毛非常短。短鞭毛很少有轴丝,但会组装异位微管和外致密纤维,并积累组装不当的纤维鞘蛋白。因此,IFT对于哺乳动物精子鞭毛的形成至关重要,但对其维持并非必需。