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Updated: Mar 19, 2026
Author Spotlight: A Live Cell Imaging Technique to Study Calcium Signaling and Acrosome Exocytosis in Mouse Sperm
Published on: October 13, 2023
Biogenesis of sperm acrosome is regulated by pre-mRNA alternative splicing of Acrbp in the mouse
Yoshinori Kanemori1, Yoshitaka Koga2, Mai Sudo2
1Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan; PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan;
Abstract:
Proper biogenesis of a sperm-specific organelle, the acrosome, is essential for gamete interaction. An acrosomal matrix protein, ACRBP, is known as a proacrosin-binding protein. In mice, two forms of ACRBP, wild-type ACRBP-W and variant ACRBP-V5, are generated by pre-mRNA alternative splicing of Acrbp Here, we demonstrate the functional roles of these two ACRBP proteins. ACRBP-null male mice lacking both proteins showed a severely reduced fertility, because of malformation of the acrosome. Notably, ACRBP-null spermatids failed to form a large acrosomal granule, leading to the fragmented structure of the acrosome. The acrosome malformation was rescued by transgenic expression of ACRBP-V5 in ACRBP-null spermatids. Moreover, exogenously expressed ACRBP-W blocked autoactivation of proacrosin in the acrosome. Thus, ACRBP-V5 functions in the formation and configuration of the acrosomal granule during early spermiogenesis. The major function of ACRBP-W is to retain the inactive status of proacrosin in the acrosome until acrosomal exocytosis.
Insights
Two forms of acrosomal matrix protein (ACRBP) play distinct roles in sperm development. ACRBP-V5 is crucial for acrosome formation, while ACRBP-W prevents premature activation of enzymes essential for fertilization.
Area of Science:
- Reproductive Biology
- Spermatogenesis
- Molecular Biology
Background:
- Acrosome biogenesis is vital for successful fertilization.
- Acrosomal matrix protein (ACRBP) binds proacrosin, a key enzyme.
- Two ACRBP forms, ACRBP-W and ACRBP-V5, arise from alternative splicing.
Purpose of the Study:
- To elucidate the distinct functional roles of ACRBP-W and ACRBP-V5 in sperm.
- To investigate the impact of ACRBP deficiency on male fertility and acrosome formation.
Main Methods:
- Generation and analysis of ACRBP-null male mice.
- Transgenic rescue experiments expressing ACRBP-V5.
- Assessment of acrosome morphology and proacrosin activation.
Main Results:
- ACRBP-null mice exhibited severely reduced fertility due to acrosome malformation.
- ACRBP-null spermatids failed to form proper acrosomal granules.
- Transgenic ACRBP-V5 rescued acrosome malformation; ACRBP-W inhibited proacrosin autoactivation.
Conclusions:
- ACRBP-V5 is essential for acrosomal granule formation and structure during spermiogenesis.
- ACRBP-W maintains proacrosin in an inactive state within the acrosome until fertilization.
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