Abstract
The sperm acrosome is essential for sperm-egg fusion and is often defective in men with nonobstructive infertility. Here we report that male mice with a null mutation in Hrb are infertile and display round-headed spermatozoa that lack an acrosome. In wild-type spermatids, Hrb is associated with the cytosolic surface of proacrosomic transport vesicles that fuse to create a single large acrosomic vesicle at step 3 of spermiogenesis. Although proacrosomic vesicles form in spermatids that lack Hrb, the vesicles are unable to fuse, blocking acrosome development at step 2. We conclude that Hrb is required for docking and/or fusion of proacrosomic vesicles during acrosome biogenesis.
MeSH terms
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Acrosome / chemistry
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Acrosome / physiology*
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Acrosome / ultrastructure*
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Adaptor Protein Complex alpha Subunits
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Animals
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Calcium-Binding Proteins / analysis
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Calcium-Binding Proteins / metabolism
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Carrier Proteins / analysis
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Carrier Proteins / physiology*
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Female
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Fertilization in Vitro
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Gene Targeting
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Golgi Apparatus / chemistry
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Intracellular Signaling Peptides and Proteins
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Male
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Membrane Proteins / metabolism
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Mice
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Mice, Knockout
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Microscopy, Confocal
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Microscopy, Electron
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Microscopy, Immunoelectron
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Mutation
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Nuclear Pore Complex Proteins / analysis
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Nuclear Pore Complex Proteins / deficiency
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Nuclear Pore Complex Proteins / genetics
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Nuclear Pore Complex Proteins / physiology*
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Phosphoproteins / analysis
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Phosphoproteins / metabolism
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RNA-Binding Proteins*
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Sperm Count
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Sperm Motility
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Sperm-Ovum Interactions
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Spermatids / chemistry
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Spermatids / physiology*
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Spermatids / ultrastructure
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Spermatogenesis*
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Spermatozoa / physiology
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Spermatozoa / ultrastructure
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Transport Vesicles / chemistry
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Transport Vesicles / physiology*
Substances
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AGFG1 protein, human
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Adaptor Protein Complex alpha Subunits
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Agfg1 protein, mouse
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Calcium-Binding Proteins
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Carrier Proteins
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Eps15 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nuclear Pore Complex Proteins
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Phosphoproteins
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RNA-Binding Proteins