Intraflagellar transport is essential for mammalian spermiogenesis but is absent in mature sperm.
Intraflagellar transport is essential for mammalian spermiogenesis but is absent in mature sperm.
复制标题
DOI：
10.1091/mbc.e15-08-0578
复制
发表时间：
2015-12-01
影响因子：
3.3
通讯作者：
Witman GB
中科院分区：
文献类型：
--
作者：
San Agustin JT;Pazour GJ;Witman GB
鞭毛内运输（IFT）对于大多数纤毛的组装和维持是必要的，但在某些生物体中配子体鞭毛除外。小鼠精子鞭毛的组装需要IFT，而IFT的缺陷会导致雄性不育。然而，成熟精子缺乏IFT蛋白，因此不需要IFT来维持轴素。果蝇精子的不寻常之处在于它们不需要鞭毛内运输（IFT）系统来组装鞭毛。在小鼠中，IFT蛋白在睾丸中非常丰富，但我们在这里显示成熟精子完全缺乏它们，这使得IFT对哺乳动物精子发育的重要性尚不清楚。为了解决这个问题，我们对Ift88Tg737Rpw小鼠的精子发生和生育能力进行了表征。这只小鼠在编码IFT颗粒的IFT88亚基的基因中有一个半胚突变。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，剩余的精子完全没有鞭毛或鞭毛很短。短鞭毛很少有轴突，但聚集异位微管和外层致密纤维，并积聚不正确组装的纤维鞘蛋白。因此，IFT对哺乳动物精子鞭毛的形成是必不可少的，而不是维持。
Intraflagellar transport (IFT) is necessary for the assembly and maintenance of most cilia, with the exception of gametic flagella in some organisms. IFT is required for assembly of mouse sperm flagella, and defects in IFT lead to male infertility. However, mature sperm lack IFT proteins and thus do not require IFT for maintenance of the axoneme. 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 Ift88Tg737Rpw 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.