Two Functional Forms of ACRBP/sp32 Are Produced by Pre-mRNA Alternative Splicing in the Mouse1

Kanemori, Yoshinori; Ryu, Jin‐Hyeob; Sudo, Mai; Niida-Araida, Yasushi; Kodaira, Kunihiko; Takenaka, Mika; Kohno, Naoki; Sugiura, Saiko; Kashiwabara, Shin‐ichi; Baba, Tadashi

doi:10.1095/biolreprod.112.107425

Cited by 24 publications

(39 citation statements)

References 28 publications

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“…The frequencies of the midpiece bending in type 1/type 2 and type 3 Acrbp −/− sperm were modestly and severely reduced, respectively. The abnormal bending motion in Acrbp −/− sperm may be due to the deformed structure of the acrosome because ACRBP is localized exclusively in the acrosome (18). We could not examine the type 4 sperm, because of the entwinement of the midpiece around the nucleus (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…ACRBP also has been identified as a member of the cancer/testis antigen family; ACRBP is normally expressed exclusively in the testis, but is also expressed in a wide range of different tumor types, including bladder, breast, liver, and lung carcinomas (15)(16)(17). Mammalian ACRBP is initially synthesized as a ∼60-kDa precursor protein (ACRBP-W) in spermatogenic cells, and the 32-kDa mature ACRBP (ACRBP-C) is posttranslationally produced by removal of the N-terminal half of the precursor ACRBP-W during spermatogenesis and/or epididymal maturation of sperm (14,18). In the mouse, two forms of Acrbp mRNA, wild-type Acrbp-W and variant Acrbp-V5 mRNAs, are produced by pre-mRNA alternative splicing of Acrbp (18).…”

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confidence: 99%

“…Mammalian ACRBP is initially synthesized as a ∼60-kDa precursor protein (ACRBP-W) in spermatogenic cells, and the 32-kDa mature ACRBP (ACRBP-C) is posttranslationally produced by removal of the N-terminal half of the precursor ACRBP-W during spermatogenesis and/or epididymal maturation of sperm (14,18). In the mouse, two forms of Acrbp mRNA, wild-type Acrbp-W and variant Acrbp-V5 mRNAs, are produced by pre-mRNA alternative splicing of Acrbp (18). Similarly to other mammalian ACRBP-W, mouse ACRBP-W starts to be synthesized in pachytene spermatocytes and immediately processed into ACRBP-C (Fig.…”

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confidence: 99%

“…The intron 5-retaining splice variant mRNA produces a predominant form of ACRBP, ACRBP-V5, that is also present in pachytene spermatocytes and round spermatids, but is absent in elongating spermatids (18). Functional analysis in vitro reveals that ACRBP-V5 and ACRBP-C possess a different domain capable of binding each of two segments in the C-terminal region of proACR (18). Moreover, autoactivation of proACR is remarkably accelerated by the presence of Significance Mammalian sperm possess a Golgi-derived exocytotic organelle, the acrosome, located on the apical region of the head.…”

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confidence: 99%

“…ACRBP-C (14,18). Thus, we postulated that, at least in the mouse, ACRBP-V5 and ACRBP-C may differentially function in the transport/packaging of proACR into the acrosomal granule during spermiogenesis and in the promotion of ACR release from the acrosome during acrosomal exocytosis, respectively.…”

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

Kanemori

Koga

Sudo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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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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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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

Kanemori

Koga

Sudo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Modulation of alternative splicing by anticancer drugs

et al. 2015

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Pre-mRNA alternative splicing is a highly regulated process that generates multiple mRNAs coding different protein isoforms. These protein isoforms may have similar, different, or even opposing functions. Expression of genes involved in cell growth and apoptosis are often altered in cancer cells. Studying the alternative splicing patterns of these important genes can have a significant role in the treatment of cancer. Resistance to chemotherapy is often caused due to overexpression of anti-apoptotic isoforms or suppression of pro-apoptotic isoforms. Anticancer drugs are capable of modulating the expression of different transcript isoforms of genes. Some anticancer drugs induce pro-apoptotic transcript isoforms leading to apoptosis or at least sensitizing cells to chemotherapy. However, in other cases, they shift the splicing toward isoforms having anti-apoptotic functions thus conferring resistance to chemotherapy. This mini-review summarizes the current knowledge about alternative splicing of some important genes involved in cancers. Furthermore, splicing patterns as well as generation of functionally distinct protein isoforms have also been mentioned. Role of various anticancer drugs in modulating alternative splicing of these genes has been reported along with a brief insight into their mechanism of action. Modulation of alternative splicing toward production of pro-apoptotic isoforms of various genes by anticancer drugs offers great therapeutic potential in the treatment of cancer.

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Human globozoospermia‐related genes and their role in acrosome biogenesis

Moreno

2022

WIREs Mechanisms of Disease

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The mammalian acrosome is a secretory vesicle attached to the sperm nucleus whose fusion with the overlying plasma membrane is required to achieve fertilization. Acrosome biogenesis starts during meiosis, but it lasts through the entire process of haploid cell differentiation (spermiogenesis). Acrosome biogenesis is a stepwise process that involves membrane traffic from the Golgi apparatus, but it also seems that the lysosome/endosome system participates in this process. Defective sperm head morphology is accompanied by defective acrosome shape and function, and patients with these characteristics are infertile or subfertile. The most extreme case of acrosome biogenesis failure is globozoospermia syndrome, which is primarily characterized by the presence of round‐headed spermatozoa without acrosomes with cytoskeleton defects around the nucleus and infertility. Several genes participating in acrosome biogenesis have been uncovered using genetic deletions in mice, but only a few of them have been found to be deleted or modified in patients with globozoospermia. Understanding acrosome biogenesis is crucial to uncovering the molecular basis of male infertility and developing new diagnostic tools and assisted reproductive technologies that may help infertile patients through more effective treatment techniques. This article is categorized under: Reproductive System Diseases > Environmental Factors Infectious Diseases > Stem Cells and Development Reproductive System Diseases > Molecular and Cellular Physiology

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Two Functional Forms of ACRBP/sp32 Are Produced by Pre-mRNA Alternative Splicing in the Mouse1

Cited by 24 publications

References 28 publications

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

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

Modulation of alternative splicing by anticancer drugs

Human globozoospermia‐related genes and their role in acrosome biogenesis

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