Loss of the deglutamylase CCP5 perturbs multiple steps of spermatogenesis and leads to male infertility
Sperm cells are highly specialized mammalian cells, and their biogenesis requires unique intracellular structures. Perturbations of spermatogenesis often lead to male infertility. Here we assess the role of a posttranslational modification of tubulin, glutamylation, in spermatogenesis. We show that mice lacking the tubulin deglutamylase CCP5 do not form functional sperm. Spermatids accumulate polyglutamylated tubulin, accompanied by the occurrence of disorganized microtubule arrays, in particular the sperm manchette, 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, and essential regulator of several microtubule-based functions during spermatogenesis. This makes enzymes involved in glutamylation prime candidates for genes involved in male sterility.