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Cell Mol Life Sci. 2019 Jun 19. doi: 10.1007/s00018-019-03192-4. [Epub ahead of print]

Vps13b is required for acrosome biogenesis through functions in Golgi dynamic and membrane trafficking.

Author information

1
Inserm, UMR1231, Equipe GAD, Bâtiment B3, Université de Bourgogne Franche Comté, 15 boulevard du Maréchal de Lattre de Tassigny, 21000, Dijon Cedex, France. romain.dacosta@chu-dijon.fr.
2
FHU TRANSLAD, CHU Dijon, 21000, Dijon, France. romain.dacosta@chu-dijon.fr.
3
Inserm, UMR1231, Equipe GAD, Bâtiment B3, Université de Bourgogne Franche Comté, 15 boulevard du Maréchal de Lattre de Tassigny, 21000, Dijon Cedex, France.
4
FHU TRANSLAD, CHU Dijon, 21000, Dijon, France.
5
Laboratoire de Biologie de la Reproduction, Hôpital François Mitterrand, Université de Bourgogne, 21000, Dijon, France.
6
Centre de Référence Maladies Génétique à Expression Cutanée MAGEC-Mosaique, CHU Dijon, Dijon, France.
7
Plateforme d'Imagerie Cellulaire CellImaP/DimaCell, Inserm LNC UMR1231, 21000, Dijon, France.
8
Centre de Référence Déficiences Intellectuelles de Causes Rares, CHU Dijon, 21000, Dijon, France.
9
Centre de Référence Anomalies du Développement et Syndromes Malformatifs, CHU Dijon, 21000, Dijon, France.

Abstract

The sperm acrosome is a lysosome-related organelle that develops using membrane trafficking from the Golgi apparatus as well as the endolysosomal compartment. How vesicular trafficking is regulated in spermatids to form the acrosome remains to be elucidated. VPS13B, a RAB6-interactor, was recently shown involved in endomembrane trafficking. Here, we report the generation of the first Vps13b-knockout mouse model and show that male mutant mice are infertile due to oligoasthenoteratozoospermia. This phenotype was explained by a failure of Vps13b deficient spermatids to form an acrosome. In wild-type spermatids, immunostaining of Vps13b and Rab6 revealed that they transiently locate to the acrosomal inner membrane. Spermatids lacking Vps13b did not present with the Golgi structure that characterizes wild-type spermatids and showed abnormal targeting of PNA- and Rab6-positive Golgi-derived vesicles to Eea1- and Lamp2-positive structures. Altogether, our results uncover a function of Vps13b in the regulation of the vesicular transport between Golgi apparatus, acrosome, and endolysosome.

KEYWORDS:

Acrosomogenesis; Endosome; Globozoospermia; Lysosome; Male infertility; Oligospermia; Spermatogenesis; Spermiogenesis; Vesicular transport

PMID:
31218450
DOI:
10.1007/s00018-019-03192-4

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