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Absence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus.
Development. 2012 Aug; 139(16):2955-65.D

Abstract

Sperm-head elongation and acrosome formation, which take place during the last stages of spermatogenesis, are essential to produce competent spermatozoa that are able to cross the oocyte zona pellucida and to achieve fertilization. During acrosome biogenesis, acrosome attachment and spreading over the nucleus are still poorly understood and to date no proteins have been described to link the acrosome to the nucleus. We recently demonstrated that a deletion of DPY19L2, a gene coding for an uncharacterized protein, was responsible for a majority of cases of type I globozoospermia, a rare cause of male infertility that is characterized by the exclusive production of round-headed acrosomeless spermatozoa. Here, using Dpy19l2 knockout mice, we describe the cellular function of the Dpy19l2 protein. We demonstrate that the protein is expressed predominantly in spermatids with a very specific localization restricted to the inner nuclear membrane facing the acrosomal vesicle. We show that the absence of Dpy19l2 leads to the destabilization of both the nuclear dense lamina (NDL) and the junction between the acroplaxome and the nuclear envelope. Consequently, the acrosome and the manchette fail to be linked to the nucleus leading to the disruption of vesicular trafficking, failure of sperm nuclear shaping and eventually to the elimination of the unbound acrosomal vesicle. Finally, we show for the first time that Dpy19l3 proteins are also located in the inner nuclear envelope, therefore implying that the Dpy19 proteins constitute a new family of structural transmembrane proteins of the nuclear envelope.

Authors+Show Affiliations

Université Joseph Fourier, Grenoble F-38000, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22764053

Citation

Pierre, Virginie, et al. "Absence of Dpy19l2, a New Inner Nuclear Membrane Protein, Causes Globozoospermia in Mice By Preventing the Anchoring of the Acrosome to the Nucleus." Development (Cambridge, England), vol. 139, no. 16, 2012, pp. 2955-65.
Pierre V, Martinez G, Coutton C, et al. Absence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus. Development. 2012;139(16):2955-65.
Pierre, V., Martinez, G., Coutton, C., Delaroche, J., Yassine, S., Novella, C., Pernet-Gallay, K., Hennebicq, S., Ray, P. F., & Arnoult, C. (2012). Absence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus. Development (Cambridge, England), 139(16), 2955-65. https://doi.org/10.1242/dev.077982
Pierre V, et al. Absence of Dpy19l2, a New Inner Nuclear Membrane Protein, Causes Globozoospermia in Mice By Preventing the Anchoring of the Acrosome to the Nucleus. Development. 2012;139(16):2955-65. PubMed PMID: 22764053.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Absence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus. AU - Pierre,Virginie, AU - Martinez,Guillaume, AU - Coutton,Charles, AU - Delaroche,Julie, AU - Yassine,Sandra, AU - Novella,Caroline, AU - Pernet-Gallay,Karin, AU - Hennebicq,Sylviane, AU - Ray,Pierre F, AU - Arnoult,Christophe, Y1 - 2012/07/04/ PY - 2012/7/6/entrez PY - 2012/7/6/pubmed PY - 2012/10/17/medline SP - 2955 EP - 65 JF - Development (Cambridge, England) JO - Development VL - 139 IS - 16 N2 - Sperm-head elongation and acrosome formation, which take place during the last stages of spermatogenesis, are essential to produce competent spermatozoa that are able to cross the oocyte zona pellucida and to achieve fertilization. During acrosome biogenesis, acrosome attachment and spreading over the nucleus are still poorly understood and to date no proteins have been described to link the acrosome to the nucleus. We recently demonstrated that a deletion of DPY19L2, a gene coding for an uncharacterized protein, was responsible for a majority of cases of type I globozoospermia, a rare cause of male infertility that is characterized by the exclusive production of round-headed acrosomeless spermatozoa. Here, using Dpy19l2 knockout mice, we describe the cellular function of the Dpy19l2 protein. We demonstrate that the protein is expressed predominantly in spermatids with a very specific localization restricted to the inner nuclear membrane facing the acrosomal vesicle. We show that the absence of Dpy19l2 leads to the destabilization of both the nuclear dense lamina (NDL) and the junction between the acroplaxome and the nuclear envelope. Consequently, the acrosome and the manchette fail to be linked to the nucleus leading to the disruption of vesicular trafficking, failure of sperm nuclear shaping and eventually to the elimination of the unbound acrosomal vesicle. Finally, we show for the first time that Dpy19l3 proteins are also located in the inner nuclear envelope, therefore implying that the Dpy19 proteins constitute a new family of structural transmembrane proteins of the nuclear envelope. SN - 1477-9129 UR - https://www.unboundmedicine.com/medline/citation/22764053/Absence_of_Dpy19l2_a_new_inner_nuclear_membrane_protein_causes_globozoospermia_in_mice_by_preventing_the_anchoring_of_the_acrosome_to_the_nucleus_ L2 - http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=22764053 DB - PRIME DP - Unbound Medicine ER -