Alteration in the processing of the ACRBP/sp32 protein and sperm head/acrosome malformations in proprotein convertase 4 (PCSK4) null mice

Tardif, Steve; Guyonnet, Benoît; Cormier, Nathaly; Cornwall, Gail A.

doi:10.1093/molehr/gas009

Cited by 36 publications

(36 citation statements)

References 33 publications

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“…Importantly, PCSK4-deficient testicular and epididymal sperm displayed aberrant shape of the acrosome; acrosomal components, including unprocessed ACRBP-W, were insufficiently spread over the acrosomal matrix, but rather were localized as acrosomal granule-like punctate structures near the apical region of the acrosome [29]. Because our data indicate that the processing of ACRBP-W into ACRBP-C rapidly occurs in postmeiotic spermatogenic cells (Fig.…”

Section: Kanemori Et Almentioning

confidence: 67%

“…sperm function [27,28], the loss of PCSK4 resulted in the failure to convert ACRBP-W into ACRBP-C, despite the absence of consensus sequences for the enzymatic cleavage site [29]. Importantly, PCSK4-deficient testicular and epididymal sperm displayed aberrant shape of the acrosome; acrosomal components, including unprocessed ACRBP-W, were insufficiently spread over the acrosomal matrix, but rather were localized as acrosomal granule-like punctate structures near the apical region of the acrosome [29].…”

Section: Kanemori Et Almentioning

confidence: 99%

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

Kanemori

Ryu

Sudo

et al. 2013

Biology of Reproduction

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ACRBP/sp32 is a binding protein specific for the precursor (pro-ACR) and intermediate forms of sperm serine protease ACR. In this study, we examined the expression pattern, localization, and possible role of mouse ACRBP in spermatogenic cells and epididymal sperm. Unlike other mammalian ACRBPs, two forms of Acrbp mRNA-wild-type Acrbp-W and variant Acrbp-V5 mRNAs-were generated by alternative splicing of Acrbp in the mouse. ACRBP-W was synthesized in pachytene spermatocytes and haploid spermatids and immediately processed into a mature protein, ACRBP-C, by removal of the N-terminal half. The intron 5-retaining splice variant mRNA produced a predominant form of ACRBP, ACRBP-V5, that was present in pachytene spermatocytes and round spermatids, but was absent in elongating spermatids. ACRBP-W and ACRBP-V5 were both colocalized with pro-ACR in the acrosomal granules of early round spermatids, whereas the sperm acrosome contained only ACRBP-C. Glutathione S-transferase pull-down assays revealed that ACRBP-V5 and ACRBP-C possess a different domain capable of binding each of two segments in the C-terminal region of pro-ACR. Moreover, autoactivation of pro-ACR was remarkably accelerated by the presence of ACRBP-C. These results suggest that ACRBP-V5 and ACRBP-C may function in the transport/packaging of pro-ACR into acrosomal granules during spermiogenesis and in the promotion of ACR release from the acrosome during acrosomal exocytosis, respectively.

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Section: Kanemori Et Almentioning

confidence: 67%

Section: Kanemori Et Almentioning

confidence: 99%

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

Kanemori

Ryu

Sudo

et al. 2013

Biology of Reproduction

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“…**P < 0.05; *P < 0.01. as PC4 or SPC5)-null mice (48): the abnormally eccentric localization of the acrosomal granule and the fragmented structure of acrosome. The loss of PCSK4 results in the failure of ACRBP-W proteolytic processing into the mature ACRBP-C in testicular and epididymal sperm (48), implying that the failure of ACRBP-W processing in Pcsk4 −/− spermatids may be attributed to abnormal formation of the acrosome. However, despite the phenotypical similarity between the Pcsk4 −/− and KO W-TG mice, exogenously expressed ACRBP-W in spermatids and sperm is normally converted into ACRBP-C (Figs.…”

Section: Discussionmentioning

confidence: 99%

Biogenesis of sperm acrosome is regulated by pre-mRNA alternative splicing ofAcrbpin 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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“…Furthermore, exposure of spermatozoa to a peptide inhibitor of PCSK4 resulted in decreased ADAM2 processing [ 76 ]. Finally, mice lacking PCSK4 showed reduced levels of sperm ACRBP protein processing in the epididymis, suggesting that several sperm associated proteins may be PCSK4 substrates [ 77 ]. Recent evidence suggests that in addition to PCSK4 present in spermatozoa, a population of PCSK4 is present in the epididymal fl uid and may also contribute to sperm protein processing [ 78 ] [Cornwall, unpublished observations].…”

Section: Protein Processingmentioning

confidence: 99%

Role of Posttranslational Protein Modifications in Epididymal Sperm Maturation and Extracellular Quality Control

Cornwall

2014

Advances in Experimental Medicine and Biology

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The epididymal lumen is a complex microenvironment in which spermatozoa acquire motility and fertility. Spermatozoa are synthetically inactive and therefore the maturation process requires their interaction with proteins that are synthesized and secreted in a highly regionalized manner by the epididymal epithelium. In addition to the integration of epididymal secretory proteins, posttranslational modifications of existing sperm proteins are important for sperm maturation and acquisition of fertilizing potential. Phosphorylation, glycosylation, and processing are several of the posttranslational modifications that sperm proteins undergo during epididymal transit resulting in changes in protein function and localization ultimately leading to mature spermatozoa. In addition to these well-characterized modifications, protein aggregation and cross-linking also occur within the epididymal lumen and may represent unique mechanisms for controlling protein function including that for maturation as well as for extracellular quality control.

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Alteration in the processing of the ACRBP/sp32 protein and sperm head/acrosome malformations in proprotein convertase 4 (PCSK4) null mice

Cited by 36 publications

References 33 publications

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

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

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

Role of Posttranslational Protein Modifications in Epididymal Sperm Maturation and Extracellular Quality Control

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