Institut Curie, PSL Research University, CNRS UMR3348, F-91405 Orsay, France.
Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, F-91405 Orsay, France.
J Cell Sci. 2019 Feb 7;132(3):jcs226951. doi: 10.1242/jcs.226951.
Sperm cells are highly specialized mammalian cells, and their biogenesis requires unique intracellular structures. Perturbation of spermatogenesis often leads to male infertility. Here, we assess the role of a post-translational modification of tubulin, glutamylation, in spermatogenesis. We show that mice lacking the tubulin deglutamylase CCP5 (also known as AGBL5) do not form functional sperm. In these mice, spermatids accumulate polyglutamylated tubulin, accompanied by the occurrence of disorganized microtubule arrays, in particular in the sperm manchette. Spermatids further fail to re-arrange their intracellular space and accumulate organelles and cytosol, while nuclei condense normally. Strikingly, spermatids lacking CCP5 show supernumerary centrioles, suggesting that glutamylation could control centriole duplication. We show that most of these observed defects are also present in mice in which CCP5 is deleted only in the male germ line, strongly suggesting that they are germ-cell autonomous. Our findings reveal that polyglutamylation is, beyond its known importance for sperm flagella, an essential regulator of several microtubule-based functions during spermatogenesis. This makes enzymes involved in glutamylation prime candidates for being genes involved in male sterility.
精子细胞是高度特化的哺乳动物细胞，其发生需要独特的细胞内结构。精子发生的扰动常常导致男性不育。在这里，我们评估了翻译后修饰（泛素化）在精子发生中的作用。我们发现缺乏微管去泛素化酶 CCP5（也称为 AGBL5）的小鼠不能形成有功能的精子。在这些小鼠中，精细胞积累多聚谷氨酰化的微管，伴随着微管排列紊乱的发生，特别是在精子顶体囊中。精细胞进一步不能重新排列其细胞内空间，并积累细胞器和细胞质，而核正常浓缩。引人注目的是，缺乏 CCP5 的精细胞显示出额外的中心粒，表明泛素化可以控制中心粒复制。我们表明，在仅在雄性生殖系中删除 CCP5 的小鼠中也存在这些观察到的大多数缺陷，这强烈表明它们是生殖细胞自主的。我们的研究结果表明，多聚谷氨酰化除了对精子鞭毛的已知重要性之外，还是精子发生过程中几种基于微管的功能的重要调节剂。这使得参与泛素化的酶成为涉及男性不育的基因的主要候选者。
