Loss of the deglutamylase CCP5 perturbs multiple steps of spermatogenesis and leads to male infertility - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Cell Science Année : 2018

Loss of the deglutamylase CCP5 perturbs multiple steps of spermatogenesis and leads to male infertility

Résumé

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 rearrange 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.
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Dates et versions

hal-02375075 , version 1 (21-11-2019)

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Tiziana Giordano, Sudarshan Gadadhar, Satish Bodakuntla, Jonas Straub, Sophie Leboucher, et al.. Loss of the deglutamylase CCP5 perturbs multiple steps of spermatogenesis and leads to male infertility. Journal of Cell Science, 2018, ⟨10.1242/jcs.226951⟩. ⟨hal-02375075⟩
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