Biogenesis of sperm acrosome is regulated by pre-mRNA alternative splicing of acrbp in the mouse

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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.

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Kanemori, Y., Koga, Y., Sudo, M., Kang, W., Kashiwabara, S. I., Ikawa, M., … Baba, T. (2016). Biogenesis of sperm acrosome is regulated by pre-mRNA alternative splicing of acrbp in the mouse. Proceedings of the National Academy of Sciences of the United States of America, 113(26), E3696–E3705. https://doi.org/10.1073/pnas.1522333113

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