Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The guinea pig sperm protein fertilin (previously termed PH-30) plays an important role in sperm-egg fusion, and was the first recognized membrane-anchored metalloprotease/disintegrin protein. Fertilin is a heterodimeric glycoprotein which undergoes at least two distinct proteolytic processing steps. Fertilin alpha is processed first, in the testis, whereas fertilin beta is processed separately during sperm maturation in the epididymis. The final processing of fertilin beta occurs immediately adjacent to its predicted integrin ligand domain, and exposes an epitope recognized by a fusion blocking monoclonal antibody. Here, we demonstrate that one or more serine protease activities associated with testicular sperm can process fertilin beta in vitro in a fashion that closely mimics the processing pattern observed in vivo during epididymal sperm maturation. In contrast, several proteases that were added to testicular sperm did not mimic the pattern observed in vivo. These findings raise the intriguing possibility that a fertilin beta converting protease(s) active in vivo may originate from sperm, instead of from the epididymal epithelium. Further, we show that fertilin alpha is most likely processed intracellularly in the secretory pathway based on three observations: (i) only processed fertilin alpha, but not the precursor pro-alpha can be cell-surface biotinylated; (ii) some processed fertilin alpha is sensitive to endoglycosidase H, suggesting cleavage occurs prior to the medial Golgi apparatus; (iii) a reanalysis of the N-terminus of processed fertilin alpha showed that the proteolytic cleavage site is next to four arginine residues, a consensus sequence for intracellular subtilysin type pro-protein convertases. The N-terminal sequence analysis further showed that processed fertilin alpha contains an intact membrane anchored disintegrin domain, and not a truncated disintegrin domain as reported previously (Blobel, C. P., Wolfsberg, T. G., Turck, C. W., Myles, D. G., Primakoff, P., and White, J. M., Nature 356, 248-252, 1992). Proteolytic processing is thought to play an important role in regulating the function of fertilin, and the present study represents a first step toward a better understanding of protease activities involved in the maturation of fertilin, and potentially other sperm surface proteins.
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PMID:Evidence for distinct serine protease activities with a potential role in processing the sperm protein fertilin. 935 77

Monoclonal antibody, (mAb) D7G3, directed to human spermatozoa and cross-reactive with mouse and rat spermatozoa was found to be a sperm agglutinating antibody. It reacted with antigen present on the post acrosomal region of human spermatozoa and acrosomal region of mouse spermatozoa. The antigen reacting with mAb D7G3 was localized in mouse testicular germ cells and Sertoli cells. It was also localized in the epithelium and spermatozoa of the caput, corpus and cauda epididymides. In addition, the antigen was detected in the epithelial cells and secretions of the prostate and seminal vesicle. The mAb D7G3 reacted with a band of molecular mass 16 kDa in testicular and epididymal sperm and protein preparations of ventral prostate. In the seminal vesicle, an additional band of molecular mass 36 kDa was also identified. The effect of castration on the expression of proteins was studied in the rat. Immunohistochemical localization and Western blotting experiments showed that the antigens identified by the mAb D7G3 was detectable in the epididymis, ventral prostate and seminal vesicle after two weeks of castration. In the seminal vesicle, three additional bands were identified by mAb D7G3 following castration. The expression of this antigen throughout spermatogenesis and sperm maturation indicated that it may have an important biological function. A polyclonal antiserum directed to the 16 kDa mouse epididymal sperm protein was raised in rabbits. Passive immunization of female mice with this antibody caused a significant reduction in fertility only if administered 24 hours prior to mating, indicating that the antibody inhibited a pre-fertilization event by inhibiting sperm function.
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PMID:Immunochemical characterization and antifertility effect of an androgen independent antigen of spermatozoa identified by a monoclonal antibody (D7G3). 942 47

Three nucleotide sequences encoding SP22, a protein originally identified in detergent extracts of cauda epididymal sperm, were isolated from a rat testis cDNA library. While two of these cDNA sequences differed only in their 5' untranslated regions, a third cDNA was predicted to contain an additional 13 amino acids of coding sequence. Amino acid sequences obtained following Edman degradation of purified SP22 protein and cDNA sequence data both indicated that SP22 was a member of a highly conserved and widely expressed gene family found in organisms as diverse as human and Escherichia coli. Interestingly, while a 1-kb mRNA transcript was widely expressed in somatic tissues, a unique pattern of testicular expression was observed, including the appearance of a novel 1.5-kb transcript and an increase in the abundance of the 1-kb transcript during spermatogenic cell development. Anti-SP22 peptide antiserum was shown to recognize a family of 22-kDa proteins on western blots of detergent-extracted cauda epididymal sperm protein, suggesting that multiple charge variants of SP22 coexist. Moreover, affinity-purified anti-SP22 peptide immunoglobulin localized in a highly specific manner to the anterior-ventral surface of the equatorial segment of the sperm head. This is an extremely intriguing finding as SP22 was originally shown to be highly correlated with, and predictive of, the fertilizing ability of cauda epididymal sperm. Although no conclusive function has been attributed to any members of the SP22 gene family, the localization of SP22 over a discrete region of the sperm head suggests a pivotal role in sperm-egg interactions.
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PMID:SP22: a novel fertility protein from a highly conserved gene family. 973 39

We have previously identified a hamster sperm protein, P26h, proposed to be involved in the interaction between spermatozoa and the egg's zona pellucida. In this study we investigated the mechanism of P26h accumulation on hamster spermatozoa during epididymal maturation. Immunocytochemical studies showed an accumulation of P26h on the acrosomal cap of hamster spermatozoa during epididymal transit. To document the anchoring mechanism of P26h, cauda epididymal spermatozoa were exposed to different treatments. High-salt buffered solutions were unable to remove P26h from the surface of intact spermatozoa. P26h was released in a dose-dependent manner when live spermatozoa were treated with a solution of phospholipase C specific to phosphatidylinositol. In contrast, the P26h remained associated to the sperm surface following treatment with trypsin. To document the transfer mechanisms of P26h on the maturing spermatozoa, prostasomes were isolated from the epididymal fluid and subjected to immunodetection. Western blots and immunogold studies showed that P26h was associated to epididymal prostasomes. Phospholipase C treatment performed on epididymal prostasomes, indicated that P26h also is anchored to these vesicles via a phosphatidylinositol. These results suggest that epididymal sperm maturation involves a cell to cell transfer of a phosphaditylinositol-anchored protein and that prostasomes may be implicated in this process.
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PMID:Hamster sperm antigen P26h is a phosphatidylinositol-anchored protein. 989 Jul 54

Human and monkey ejaculated sperm contain protein phosphatase-1 (PP1), PP1 inhibitor 2 (12), and glycogen synthase kinase-3 (GSK-3). Inhibition of ejaculated human sperm protein phosphatase (PP) activity with calyculin-a (CL-A) significantly stimulates motility, implicating protein dephosphorylation in motility regulation. The present experiments were conducted to characterize and compare PP and GSK-3 activity in monkey caput and caudal epididymal sperm, to determine the cellular distribution of these enzymes, and to test the thesis that epididymal sperm PP activity is inversely related to motility. Caput epididymal sperm populations, (8.8% motile) contained levels of PP activity that were >3 times as high as those of caudal spermatozoa. This PP activity was further identified by inhibitor response profiles as PP1. In both caput and caudal sperm, the majority of this PP1 activity was localized in 100,000 x g soluble fractions. Western blot analysis indicated that a portion of this difference was the result of elevated amounts of PP1 in caput compared with caudal epididymal sperm. The presence of GSK-3 activity was undetectable in 100,000 x g insoluble fractions of epididymal sperm, whereas both caput and caudal sperm soluble fractions contained GSK-3 activity, which was approximately threefold higher in caput sperm compared with caudal populations. Treatment of caput epididymal sperm from the rhesus macaque with the PP inhibitor CL-A resulted in a significant, dose-dependent increase from 8 to 38% motile cells (without any effect on their path velocity). In contrast, CL-A had no significant influence on either percent motility or path velocity of caudal epididymal sperm. Cytosolic PP1 and GSK-3 activities appear to be inversely related to the motility of monkey epididymal sperm and may have a regulatory role in the development of the potential for motility in epididymal sperm.
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PMID:Motility potential of macaque epididymal sperm: the role of protein phosphatase and glycogen synthase kinase-3 activities. 1010 Apr 73

During epididymal transit, sperm surface proteins involved in the fertilization process can be added or modified. P34H, a human epididymal-sperm protein, is proposed to be involved in the interactions between spermatozoa and the zona pellucida. We have previously demonstrated that P34H is present in men of proven fertility and is absent in 50% of men presenting with idiopathic infertility. Spermatozoa with a low amount of P34H exhibit a dramatic reduction in their ability to interact with zona pellucida. Even if the surgical success of vasectomy reversal is high, fertility is not always reestablished, possibly due to epididymal damage caused by vasectomy. In this study, western blot analyses were performed to determine the level of P34H present on spermatozoa of men who underwent vasectomy reversal. Spermatozoa obtained from different semen samples from a given individual had similar P34H levels; however, samples from different men were highly variable. When quantified by densitometric scanning, P34H levels from vasovasostomized men varied between 1.5% and 149% compared with that from a fertile donor who represented 100%. Eighteen of 25 vasovasostomized men had a P34H level lower than 30% of the normal value, while the remaining 7 males were in the normal range. Furthermore, the population of vasovasostomized men with P34H levels lower than 30% was significantly different from the control group of 19 fertile men. The high variation of P34H levels observed in vasovasostomized men did not correlate with the spermiogram values (P > 0.05). An important factor in determining sperm P34H level appears to be the period of time elapsed between the vasectomy and vasovasostomy. In summary, our results show that the P34H level varied from one man to another and that low levels of the epididymal sperm protein is associated with vasectomy reversal.
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PMID:Some vasovasostomized men are characterized by low levels of P34H, an epididymal sperm protein. 1023 56

Results from recent animal models with implications for putative human male contraceptives acting on the epididymis are reviewed. Inducing sterility by enhancing sperm transport through the epididymis has not been achieved. The induction of infertility in males of several species is easier to achieve by direct actions of drugs on sperm function (e.g. inhibition of sperm-specific isoenzymes of the glycolytic pathway by chloro-compounds) than by indirectly reducing amounts of epididymal secretions normally present in high concentration (e.g. alpha-glucosidase, L-carnitine). The former show promise for the clinic since human spermatozoa are susceptible to inhibition. On the other hand, the infertile male mice of the c-ros knock-out model demonstrate the influence of even a small region of the epididymis on fertility, so that targeting the as yet unknown epididymal factors presumably secreted in limiting amounts by this epididymal segment, is a new lead for a contraceptive. Targeting a specific sperm protein acquired in the testis, but depleted in the epididymis by toxicants that induce rapid infertility, may also lead to the discovery of new contraceptives, but these will require developing new means of organ-specific delivery of contraceptive drugs.
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PMID:Recent biochemical approaches to post-testicular, epididymal contraception. 1033 18

For successful fertilization to occur, mammalian spermatozoa must undergo a series of modifications in order to reach and penetrate the oocyte. Some of these modifications occur during passage through the epididymis, the site where spermatozoa acquire their fertilizing ability. We have previously described hamster sperm protein, P26h, which is acquired by spermatozoa during epididymal transit, and have proposed that this protein is involved in sperm-egg binding. In the present study, we report the cloning and characterization of the full-length cDNA encoding hamster P26h. A database search using the predicted hamster P26h amino acid sequence revealed 85% identity with mouse AP27 protein and porcine carbonyl reductase, members of the short-chain dehydrogenase/reductase (SDR) family of proteins. Northern blot analysis revealed a major P26h 1-kilobase transcript in the testis. No signal was detected in other somatic tissues of the hamster. In situ hybridization experiments revealed that the P26h gene was predominantly transcribed in seminiferous tubules of the testis and at a lower level in the corpus epididymidis. The identity of the cloned P26h was confirmed by immunoprecipitating in vitro-translated P26h using polyclonal antiserum raised against purified hamster sperm P26h. Taken together, these results identify P26h as a new member of the SDR family of proteins involved in the processes of mammalian gamete interactions.
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PMID:Hamster sperm protein, p26h: a member of the short-chain dehydrogenase/reductase superfamily. 1037 58

During epididymal transit, mammalian spermatozoa acquire new surface proteins that are necessary for gamete interaction. We have previously described a 34-kDa human epididymal sperm protein, P34H, that has been shown to be involved in sperm-zona pellucida interaction. In the present study, we report the cloning and characterization of the full-length complementary DNA encoding human P34H. The predicted amino acid sequence revealed 65% identity with P26h, the hamster counterpart of the P34H. The deduced P34H amino acid sequence revealed a 71% similarity with a pig lung tetrameric carbonyl reductase, a member of the short chain dehydrogenase/ reductase family proteins. Northern blot analysis revealed that P34H messenger RNA (mRNA) was highly expressed in the human epididymis, principally in the corpus region. A single 912-bp P34H transcript was detected. In situ hybridization experiments showed that the P34H mRNA was predominantly expressed in the proximal and distal sections of the corpus epididymidis. The staining was restricted to the principal cells of the epididymal epithelium. The localization of P34H mRNA was in agreement with the appearance of P34H protein along the male reproductive tract. Western blot analysis revealed that recombinant P34H expressed by a yeast expression system, is antigenically related to the native P34H sperm protein. Based on its pattern of expression and its function in one of the key steps leading to fertilization, P34H can be considered as a marker of epididymal sperm maturation in humans.
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PMID:P34H sperm protein is preferentially expressed by the human corpus epididymidis. 1038 29

Sperm surface proteins involved in fertilization can be added or modified during epididymal transit. P34H, a human epididymal-sperm protein, appears on the sperm acrosomal cap in the distal caput-proximal corpus epididymis. In previous studies, it was shown that P34H is present on spermatozoa in men of proven fertility, is absent in 50% of men presenting with idiopathic infertility, and that a high proportion of men with normospermic vasovasectomy produce spermatozoa deficient in this sperm surface protein. P34H mRNA was expressed in the principal cells of the epididymis of normal men, predominantly in the corpus region. Recently, results coming from the assisted reproductive technologies have questioned the importance of the human epididymis in sperm maturation. In order to understand the effect of obstruction on the physiological state of the human epididymis and its function in sperm maturation, we have analyzed the expression of P34H mRNA at the level of the vas deferens and along the epididymis of normal and vasectomized men. In situ hybridization experiments showed that obstruction of the vas deferens alters the pattern of P34H mRNA expression compared with the tract of normal tissues. The P34H transcript was detected in the proximal caput epididymis of vasectomized men at a much higher intensity than that observed in the same region of normal tissues, being restricted to the principal cells of the epididymal epithelium. Compared with the normal duct, the lumen of vasectomized men was distended throughout the duct and the height of the epithelium was maximal in the caput. P34H mRNA was detectable in vas deferens, was not affected by vasectomy, and a 912-base pair P34H transcript was restricted to the epithelial cells of the vas deferens. Thus, using P34H as a marker, these results show that vasectomy alters the pattern of gene expression along the human epididymis, and suggest that the vas deferens can be a major contributor to sperm maturation in certain situations.
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PMID:Effect of vasectomy on P34H messenger ribonucleic acid expression along the human excurrent duct: a reflection on the function of the human epididymis. 1115 78


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