title: Dynamic of contribution of UBPy-sorted cargo to acrosome biogenesis: effects of its derailment in a mouse model of globozoospermia, the infertile Vps54 (L967Q) mutant.
abstract: The sperm acrosome is a specialized vacuole, a member of the family of cell-specific lysosome-related organelles. Its exocytosis, the acrosome reaction, is a crucial event during fertilization. The released acrosomal contents promote sperm penetration through the investments of the oocyte, whereas the membranous components of the acrosome are involved in sperm-oocyte interaction/fusion and oocyte activation. The way that these functionally distinct acrosomal costituents reach the vacuole during its biogenesis remains poorly understood. The biosynthetic pathway and a consistent supply from the endosomal system have recently been documented. We use immunogold electron microscopy to determine the contribution of endosome cargo-sorting during step-by-step mouse acrosomogenesis. The chosen proteins of this study were UBPy (ESCRT-DUB), together with endosome compartment markers EEA1 and pallidin. The latter is described here for the first time in male germ cells. This new insight expands our knowledge of acrosomogenesis, confirming the plasticity of the endosomal system in supporting cell-type-specific functions. We also study wobbler mice, whose Vps54 mutation causes motor neuron degeneration and male infertility. Use of electron/immunoelectron microscopy and immunofluorescence enabled us to establish that the lack of an acrosome in wobbler spermatozoa is attributable to an early block in acrosome biogenesis and that the mislocalization of acrosome-destined proteins, potentially involved in the signaling events leading to oocyte activation, is possibly responsible for wobbler infertility, even after intracytoplasmic sperm injection.
authors.affiliation: Department of Biosciences, Unversity of Milan, Via Celoria 26, 20133, Milan, Italy.
authors.forename: Mariarosa
authors.initials: M
authors.lastname: Gioria
authors.affiliation: Department of Biosciences, Unversity of Milan, Via Celoria 26, 20133, Milan, Italy.
authors.forename: Maria Enrica
authors.initials: ME
authors.lastname: Pasini
authors.affiliation: Department of Biosciences, Unversity of Milan, Via Celoria 26, 20133, Milan, Italy. giovanna.berruti@unimi.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Berruti
mesh_terms: D000177:Acrosome / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D013087:Spermatids / Q000378:metabolism / Q000648:ultrastructure; D013091:Spermatogenesis; D000072660:Teratozoospermia / Q000378:metabolism* / Q000473:pathology*; D013737:Testis / Q000473:pathology / Q000648:ultrastructure; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C513476:Bloc1s6 protein, mouse; D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D033921:Vesicular Transport Proteins; C486750:Vps54 protein, mouse; D019859:Proto-Oncogene Proteins c-met; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; C541536:Usp8 protein, mouse
keywords: Acrosome; De-ubiquitinating enzyme; Endosome compartment; Globozoospermia; Lysosome-related organelle