title: Dynamics of Sun5 localization during spermatogenesis in wild type and Dpy19l2 knock-out mice indicates that Sun5 is not involved in acrosome attachment to the nuclear envelope.
abstract: The acrosome is an organelle that is central to sperm physiology and a defective acrosome biogenesis leads to globozoospermia, a severe male infertility. The identification of the actors involved in acrosome biogenesis is therefore particularly important to decipher the molecular pathogeny of globozoospermia. We recently showed that a defect in the DPY19L2 gene is present in more than 70% of globozoospermic men and demonstrated that Dpy19l2, located in the inner nuclear membrane, is the first protein involved in the attachment of the acrosome to the nuclear envelope (NE). SUN proteins serve to link the nuclear envelope to the cytoskeleton and are therefore good candidates to participate in acrosome-nucleus attachment, potentially by interacting with DPY19L2. In order to characterize new actors of acrosomal attachment, we focused on Sun5 (also called Spag4l), which is highly expressed in male germ cells, and investigated its localization during spermatogenesis. Using immunohistochemistry and Western blot experiments in mice, we showed that Sun5 transits through different cellular compartments during meiosis. In pachytene spermatocytes, it is located in a membranous compartment different to the reticulum. In round spermatids, it progresses to the Golgi and the NE before to be located to the tail/head junction in epididymal sperm. Interestingly, we demonstrate that Sun5 is not, as initially reported, facing the acrosome but is in fact excluded from this zone. Moreover, we show that in Dpy19l2 KO spermatids, upon the detachment of the acrosome, Sun5 relocalizes to the totality of the NE suggesting that the acrosome attachment excludes Sun5 from the NE facing the acrosome. Finally, Western-blot experiments demonstrate that Sun5 is glycosylated. Overall, our work, associated with other publications, strongly suggests that the attachment of the acrosome to the nucleus does not likely depend on the formation of SUN complexes.
authors.affiliation: Université Grenoble Alpes, Grenoble, F-38000, France; Equipe "Génétique, Epigénétique et thérapies de l'Infertilité" Institut Albert Bonniot, INSERM U823, Grenoble, F-38000, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Yassine
authors.affiliation: Université Grenoble Alpes, Grenoble, F-38000, France; Equipe "Génétique, Epigénétique et thérapies de l'Infertilité" Institut Albert Bonniot, INSERM U823, Grenoble, F-38000, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Escoffier
authors.affiliation: Université Grenoble Alpes, Grenoble, F-38000, France; Equipe "Génétique, Epigénétique et thérapies de l'Infertilité" Institut Albert Bonniot, INSERM U823, Grenoble, F-38000, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Abi Nahed
authors.forename: Roland Abi
authors.initials: RA
authors.lastname: Nahed
authors.affiliation: Université Grenoble Alpes, Grenoble, F-38000, France; Equipe "Génétique, Epigénétique et thérapies de l'Infertilité" Institut Albert Bonniot, INSERM U823, Grenoble, F-38000, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Pierre
authors.affiliation: Université Grenoble Alpes, Grenoble, F-38000, France; Equipe "Génétique, Epigénétique et thérapies de l'Infertilité" Institut Albert Bonniot, INSERM U823, Grenoble, F-38000, France; CHU de Grenoble, UF de Biochimie et Génétique Moléculaire, Grenoble, F-38000, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Karaouzene
authors.affiliation: Université Grenoble Alpes, Grenoble, F-38000, France; Equipe "Génétique, Epigénétique et thérapies de l'Infertilité" Institut Albert Bonniot, INSERM U823, Grenoble, F-38000, France; CHU de Grenoble, UF de Biochimie et Génétique Moléculaire, Grenoble, F-38000, France.
authors.forename: Pierre F
authors.initials: PF
authors.lastname: Ray
authors.affiliation: Université Grenoble Alpes, Grenoble, F-38000, France; Equipe "Génétique, Epigénétique et thérapies de l'Infertilité" Institut Albert Bonniot, INSERM U823, Grenoble, F-38000, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Arnoult
mesh_terms: D000177:Acrosome / Q000378:metabolism*; D000818:Animals; D006056:Golgi Apparatus / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007248:Infertility, Male; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D013087:Spermatids / Q000166:cytology / Q000378:metabolism; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism; D013091:Spermatogenesis
chemical_list: C575641:Dpy19l2 protein, mouse; D008565:Membrane Proteins; D009687:Nuclear Proteins; C559752:SUN5 protein, mouse