Localization of Kex2‐like processing endoproteases, furin and PC4, within mouse testis by in situ hybridization

Torii, Seiji; Yamagishi, Toshiyuki; Murakami, Kazuo; Nakayama, Kazuhisa

doi:10.1016/0014-5793(93)81726-g

Cited by 40 publications

(18 citation statements)

References 28 publications

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“…Cleavage of the ␤ A precursor at this site would produce a polypeptide sequence having its deduced molecular weight in exact agreement with the detected molecular mass of the nuclear polypeptide. Testicular tissue contains elevated quantities of many endoproteases (some of which are testis-specific), which are implicated in the processing of the peptides and proteins that mediate interactions between testicular cells [29][30][31]. Our earlier observations suggest that differentially processed inhibin ␣ precursors may be involved in spermatogonial differentiation and maintenance of spermatogenesis in the hamster testis [32].…”

Section: Discussionmentioning

confidence: 98%

Identification of a Nuclear Localization Signal in Activin/Inhibin βA Subunit; Intranuclear βA in Rat Spermatogenic Cells1

Bläuer

Husgafvel

Syvälä

et al. 1999

Biology of Reproduction

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Activin is a dimeric glycoprotein hormone that was initially characterized by its ability to stimulate pituitary FSH secretion and was subsequently recognized as a growth factor with diverse biological functions in a large variety of tissues. In the testis, activin has been implicated in the auto/paracrine regulation of spermatogenesis through its cognate cell membrane receptors on Sertoli and germ cells. In this study we provide evidence for intranuclear activin/inhibin betaA subunit and show its distribution in the rat seminiferous epithelium. We have shown by transient expression in HeLa cells of beta-galactosidase fusion proteins that the betaA subunit precursor contains a functional nuclear localization signal within the lysine-rich sequence corresponding to amino acids 231-244. In all stages of the rat seminiferous epithelial cycle, an intense immunohistochemical staining of nuclear betaA was demonstrated in intermediate or type B spermatogonia or primary spermatocytes in their initial stages of the first meiotic prophase, as well as in pachytene spermatocytes and elongating spermatids primarily in stages IX-XII. In some pachytene spermatocytes, the pattern of betaA immunoreactivity was consistent with the characteristic distribution of pachytene chromosomes. In the nuclei of round spermatids, betaA immunoreactivity was less intense, and in late spermatids it was localized in the residual cytoplasm, suggesting disposal of betaA before spermatozoal maturation. Immunoblot analysis of a protein extract from isolated testicular nuclei revealed a nuclear betaA species with a molecular mass of approximately 24 kDa, which is more than 1.5 times that of the mature activin betaA subunit present in activin dimers. These results suggest that activin/inhibin betaA may elicit its biological functions through two parallel signal transduction pathways, one involving the dimeric molecule and cell surface receptors and the other an alternately processed betaA sequence acting directly within the nucleus. According to our immunohistochemical data, betaA may play a significant role in the regulation of nuclear functions during meiosis and spermiogenesis.

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Section: Discussionmentioning

confidence: 98%

Identification of a Nuclear Localization Signal in Activin/Inhibin βA Subunit; Intranuclear βA in Rat Spermatogenic Cells1

Bläuer

Husgafvel

Syvälä

et al. 1999

Biology of Reproduction

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“…It is expressed in spermatocytes and round spermatids, where it is found in the acrosome and on the sperm plasma membrane overlying the acrosome (Nakayama et al, 1992;Seidah et al, 1992;Torii et al, 1993). Pc4 2/2 mice do not show any altered spermatogenesis, but spermatozoa exhibit accelerated capacitation, precocious acrosome reaction, and reduced spermatozoa-egg binding ability that is only half that of wild-type mice.…”

Section: Microscopy Research and Techniquementioning

confidence: 96%

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 3: Developmental changes in spermatid flagellum and cytoplasmic droplet and interaction of sperm with the zona pellucida and egg plasma membrane

Hermo¹,

Pelletier²,

Cyr³

et al. 2009

Microscopy Res & Technique

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Spermiogenesis constitutes the steps involved in the metamorphosis of spermatids into spermatozoa. It involves modification of several organelles in addition to the formation of several structures including the flagellum and cytoplasmic droplet. The flagellum is composed of a neck region and middle, principal, and end pieces. The axoneme composed of nine outer microtubular doublets circularly arranged to form a cylinder around a central pair of microtubules is present throughout the flagellum. The middle and principal pieces each contain specific components such as the mitochondrial sheath and fibrous sheath, respectively, while outer dense fibers are common to both. A plethora of proteins are constituents of each of these structures, with each playing key roles in functions related to the fertility of spermatozoa. At the end of spermiogenesis, a portion of spermatid cytoplasm remains associated with the released spermatozoa, referred to as the cytoplasmic droplet. The latter has as its main feature Golgi saccules, which appear to modify the plasma membrane of spermatozoa as they move down the epididymal duct and hence may be partly involved in male gamete maturation. The end product of spermatogenesis is highly streamlined and motile spermatozoa having a condensed nucleus equipped with an acrosome. Spermatozoa move through the female reproductive tract and eventually penetrate the zona pellucida and bind to the egg plasma membrane. Many proteins have been implicated in the process of fertilization as well as a plethora of proteins involved in the development of spermatids and sperm, and these are high lighted in this review.

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“…Messenger RNA for this convertase has been detected unambiguously only in spermatocytes and round spermatids of rat (16) and in round spermatids of mouse (17,18). We have disrupted its locus (Pcsk4) in mouse ES cells and have used these cells to generate mice lacking PC4.…”

mentioning

confidence: 99%

Impaired fertility in mice deficient for the testicular germ-cell protease PC4

Mbikay

Tadros

Ishida

et al. 1997

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

152

102

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PC4 is a member of the proprotein convertase family of serine proteases implicated in the processing of a variety of polypeptides including prohormones, proneuropeptides, and cell surface proteins. In rodents, PC4 transcripts have been detected in spermatocytes and round spermatids exclusively, suggesting a reproductive function for this enzyme. In an effort to elucidate this function, we have disrupted its locus (Pcsk4) by homologous recombination in embryonic stem cells and have produced mice carrying the mutation. In intercrosses of heterozygous mutant mice, there was low transmission of the mutant Pcsk4 allele to the progeny, resulting in lower than expected incidence of heterozygosity and null homozygosity. The in vivo fertility of homozygous mutant males was severely impaired in the absence of any evident spermatogenic abnormality. In vitro, the fertilizing ability of Pcsk4 null spermatozoa was also found to be significantly reduced. Moreover, eggs fertilized by these spermatozoa failed to grow to the blastocyst stage. These results suggest that PC4 in the male may be important for achieving fertilization and for supporting early embryonic development in mice.

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Localization of Kex2‐like processing endoproteases, furin and PC4, within mouse testis by in situ hybridization

Cited by 40 publications

References 28 publications

Identification of a Nuclear Localization Signal in Activin/Inhibin βA Subunit; Intranuclear βA in Rat Spermatogenic Cells1

Identification of a Nuclear Localization Signal in Activin/Inhibin βA Subunit; Intranuclear βA in Rat Spermatogenic Cells1

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 3: Developmental changes in spermatid flagellum and cytoplasmic droplet and interaction of sperm with the zona pellucida and egg plasma membrane

Impaired fertility in mice deficient for the testicular germ-cell protease PC4

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