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

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.

The histone methyltransferase SETD2 is required for expression of acrosin-binding protein 1 and protamines and essential for spermiogenesis in mice

“…S5C), which was also confirmed by RT-qPCR ( Fig. 6E) (47)(48)(49)(50). Among these genes, both Acrbp1 and Pick1 are known to be required for acrosome development, and knockout of either Acrbp1 or Pick1 led to fragmentation of the acrosome, which is similar to that seen in Setd2 mutants.…”

Kmt2b conveys monovalent and bivalent H3K4me3 in mouse spermatogonial stem cells at germline and embryonic promoters

“…In contrast, Mono-2 genes showed upregulation during spermatogenesis and were associated with known spermatid development and reproduction functions (e.g. Adam3, Wbp2nl, Acrbp, Trp63, Adad1 and Piwil1) (Aarabi et al, 2010;Connolly et al, 2005;Kanemori et al, 2016;Nishimura et al, 2001;Petre-Lazar et al, 2007;Reuter et al, 2011;Shamsadin et al, 1999;Yu et al, 2000) (Fig. 4A,B, Table S2).…”

Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility

“…An acrosome is a vesicle under the sperm membrane and above the nucleus, in the anterior part of the sperm head, that contains pivotal enzymes involved in sperm penetration into the oocyte [14,15]. The integrity of the inner acrosome membrane (IAM) (lying external to the nuclear membrane), the outer acrosome membrane (OAM) (placed below the plasma membrane), and the equatorial segment (ES) (the meeting point between the IAM and the OAM) is important for the acrosome reaction (AR) [16].…”

“…Commonly, paternally-imprinted genes are believed to act as embryo/fetal-growth promoters, while, conversely, maternally-imprinted ones oppose the embryo's growth [26]. Transcription is first detectable in the male pronucleus and, in humans, a transcription burst happens between the four-cell and eight-cell embryo stages, when the embryo gene activation (EGA) starts [15]. Hence, before EGA, preimplantation embryo development is only sustained by the sperm and oocyte-derived transcriptome and proteome, whose qualitative or quantitative alteration might cause embryonic development arrest.…”