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J Cell Sci. 2019 Feb 7;132(3). pii: jcs226951. doi: 10.1242/jcs.226951.

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

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Institut Curie, PSL Research University, CNRS UMR3348, F-91405 Orsay, France.
Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, F-91405 Orsay, France.
Cell Biology and Electron Microscopy, University of Bayreuth, 95440 Bayreuth, Germany.
Université Grenoble Alpes, Grenoble, F-38000, France.
Institute for Advanced Biosciences INSERM U1209, CNRS UMR5309, Grenoble, F-38000, France.
Institut Curie, PSL Research University, Department of Genetics, F-75005, Paris, France.
Inserm U1216, Grenoble Institut des Neurosciences, GIN, Grenoble, F-38000, France.
Université Paris Descartes, Sorbonne Paris Cité, F-75005, Paris, France.
Institut Curie, PSL Research University, CNRS UMR3348, F-91405 Orsay, France


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.


Axoneme; Basal body; Sperm development; Tubulin code; Tubulin glutamylation; Tubulin post-translational modifications

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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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