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

Yoshinori Kanemori, Yoshitaka Koga, Mai Sudo, Woojin Kang, Shin Ichi Kashiwabara, Masahito Ikawa, Hidetoshi Hasuwa, Kiyoshi Nagashima, Yu Ishikawa, Narumi Ogonuki, Atsuo Ogura, Tadashi Baba

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17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)E3696-E3705
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number26
DOIs
Publication statusPublished - 2016 Jun 28

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Keywords

  • Acrosomal biogenesis
  • Alternative splicing
  • Fertilization
  • Mouse
  • Spermiogenesis

ASJC Scopus subject areas

  • General

Cite this

Kanemori, Y., Koga, Y., Sudo, M., Kang, W., Kashiwabara, S. I., Ikawa, M., Hasuwa, H., Nagashima, K., Ishikawa, Y., Ogonuki, N., Ogura, A., & 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