Membrane cofactor protein (MCP, CD46) in seminal plasma and on spermatozoa in normal and “sterile” subjects

Seya, Tsukasa; Hara, Tomoko; Matsumoto, Misako; Kiyohara, Hisakazu; Nakanishi, Isao; Kinouchi, Toshiaki; Okabe, Masaru; Shimizu, Akira; Akedo, Hitoshi

doi:10.1002/eji.1830230620

Cited by 52 publications

(49 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its distribution is limited to the inner acrosomal membrane of murine spermatozoa and its expression is induced by the acrosomal reaction (N. Inoue, M. Nomura, M. Okabe and T. Seya, unpublished work), as is the case with human CD46 expressed in testis [14,15]. These findings with murine CD46 support reports detailing the unique structural and functional properties of CD46 expressed on human sperm [16,17], which is distinct from the ubiquitous isoforms of human CD46 [1,2]. One possible interpretation of these findings is that sperm CD46 may act as an egg-binding protein expressed on the inner acrosomal membrane.…”

Section: Introductionsupporting

confidence: 81%

“…Many groups have speculated that human CD46 is a fertilization-related protein, based on indirect evidence related to its structure and biology. These include its sperm-dominant high expression of protein [14,15], its lack of charged sugars [16,17], its limited distribution to the inner acrosomal membrane until the acrosomal reaction, when it is expressed on the surface of sperm [18], and its deficiency possibly being related to ideopathic infertility [47]. In addition, although monoclonal antibodies against CD46 were reported to block human sperm binding to hamster eggs or to human eggs [18,19], the inhibition of binding was always incomplete.…”

Section: Discussionmentioning

confidence: 99%

“…The murine CD46 has only one Ser\Thr-rich (ST) domain, ST C , similar to the human testicular isoform, whereas the ubiquitous human isoforms have combinations of the three ST domains, ST A , ST B and ST C [48,49]. Thus both human and mouse testicular germ cells\spermatozoa constitutively express only the ST C isoform of CD46 [16,17]. These results, together with our findings on testisdominant CD46 gene regulation, suggest the main function of mouse CD46 has evolved into a germ-cell\sperm-specific one.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Identification and characterization of a silencer regulatory element in the 3′-flanking region of the murine CD46 gene

Nomura

Tsujimura

Begum

et al. 2000

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

The murine membrane cofactor protein (CD46) gene is expressed exclusively in testis, in contrast to human CD46, which is expressed ubiquitously. To elucidate the mechanism of differential CD46 gene expression among species, we cloned entire murine CD46 genomic DNA and possible regulatory regions were placed in the flanking region of the luciferase reporter gene. The reporter gene assay revealed a silencing activity not in the promoter, but in the 3´-flanking region of the gene and the silencer-like element was identified within a 0.2-kb region between 0.6 and 0.8kb downstream of the stop codon. This silencer-like element was highly similar to that of the pig MHC class-I gene. The introduction of a mutation into this putative silencer element of murine CD46 resulted in an abrogation of the silencing effect. Electrophoretic mobility-shift assay indicated the presence of the binding molecule(s) for this silencer sequence in murine cell lines and tissues. A size difference of the protein–silencer-element complex was observed depending upon the solubilizers used for preparation of the nuclear extracts. A mutated silencer sequence failed to interact with the binding molecules. The level of the binding factor was lower in the testicular germ cells compared with other organs. Thus the silencer element and its binding factor may play a role in transcriptional regulation of murine CD46 gene expression. These results imply that the effects of the CD46 silencer element encompass the innate immune and reproductive systems, and in mice may determine the testicular germ-cell-dominant expression of CD46.

show abstract

Section: Introductionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification and characterization of a silencer regulatory element in the 3′-flanking region of the murine CD46 gene

Nomura

Tsujimura

Begum

et al. 2000

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

show abstract

“…The following mAbs against human CD46 were used (at 25 g/ml): J4.48 (25) and E4.3 (26) to SCR1, purchased from Beckman Coulter, Fullerton, CA and Santa Cruz Biotechnology, Santa Cruz, CA, respectively; mAbs M177 to CD46 SCR2 and M160 to CD46 SCR3 (27), kindly provided by Tsukasa Seya, Osaka Medical Center, Osaka, Japan; and mAb GB24, which recognizes SCR4 (Ref. 28 and unpublished data).…”

Section: Methodsmentioning

confidence: 99%

Interaction of Glycoprotein H of Human Herpesvirus 6 with the Cellular Receptor CD46

Santoro

Greenstone

Insinga³

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Human herpesvirus 6 (HHV-6) employs the complement regulator CD46 (membrane cofactor protein) as a receptor for fusion and entry into target cells. Like other known herpesviruses, HHV-6 encodes multiple glycoproteins, several of which have been implicated in the entry process. In this report, we present evidence that glycoprotein H (gH) is the viral component responsible for binding to CD46. Antibodies to CD46 co-immunoprecipitated an ϳ110-kDa protein band specifically associated with HHV-6-infected cells. This protein was identified as gH by selective depletion with an anti-gH monoclonal antibody, as well as by immunoblot analysis with a rabbit hyperimmune serum directed against a gH synthetic peptide. In reciprocal experiments, a monoclonal antibody against HHV-6 gH was found to co-immunoprecipitate CD46. Studies using monoclonal antibodies directed against specific CD46 domains, as well as engineered constructs lacking defined CD46 regions, demonstrated a close correspondence between the CD46 domains involved in the interaction with gH and those previously shown to be critical for HHV-6 fusion (i.e. short consensus repeats 2 and 3).Human herpesvirus 6 (HHV-6) 1 is a member of the ␤-herpesvirus subfamily (reviewed in Ref. 1). Two major HHV-6 variants, A and B, have been defined that form two segregated clusters with unique genetic, biologic, and immunologic characteristics. Primary infection with HHV-6 B occurs almost universally in early childhood and has been etiologically linked to exanthema subitum. In adult life, HHV-6 infection and/or reactivation have been associated with a wide range of diseases, including multiple sclerosis, but most of these associations have yet to be substantiated by rigorous epidemiological studies. In immunocompromised people, including those infected with human immunodeficiency virus, HHV-6 B has been implicated as an opportunistic agent that may cause life-threatening respiratory tract and central nervous system infections, as well as bone marrow or organ graft failure. Moreover, HHV-6 may act as a cofactor to accelerate progression of human immunodeficiency virus disease.The best studied members of the herpesvirus family enter cells by direct fusion with the plasma membrane in a process involving binding of viral glycoproteins to specific protein receptors on the target cell (reviewed in Ref.2). Fusion is also facilitated by virus interactions with cell surface glycosaminoglycans. Recently, we identified CD46 (membrane cofactor protein) as a cellular receptor mediating fusion and entry for both HHV-6 variants (3). This glycoprotein also serves as a cellular receptor mediating critical events in the infectious process of other human pathogens, including binding/fusion/ entry of measles virus, pilus binding of different pathogenic Neisseriae, and adhesion of group A Streptococci (reviewed in Ref. 4). CD46 is a member of the regulators of complement activation (RCA) protein family. It is a type I transmembrane glycoprotein of 45-67 kDa, expressed on most or all human nucleated ce...

show abstract

“…This protein, which possesses cofactor activity for factor I-mediated cleavage of C3b, competes with factor B in binding to C3b and decreases formation of the alternative pathway C3 convertase (C3bBb) (19,20). It has been reported that there are membraneassociated anti-complement proteins such as CD46 (MCP), CD55 (DAF), and CD59 in cell-free human and rat seminal plasma (31)(32)(33). However, a soluble type of anticomplement protein other than clusterin has not been identified in animal seminal plasma.…”

Section: Discussionmentioning

confidence: 99%

Factor H in Porcine Seminal Plasma Protects Sperm against Complement Attack in Genital Tracts

Sakaue

Takeuchi

Maeda

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

We found that factor H (FH) exists in porcine seminal plasma. Purified FH strongly inhibited serum alternative pathway complement activation against lipopolysaccharide. The molecular weight, pI, and heparin-binding activity of the purified protein were different from those of purified FH from porcine serum. The complement regulatory activity of seminal plasma FH was ϳ2-fold stronger than that of serum FH. Treatment of purified serum FH with sialidase and N-glycosidase F gave almost the same results as those of seminal plasma FH. The deletion of sialic acid from the carbohydrate chains of both FHs contributed to heparin-binding and complement regulatory activities. Results of reverse transcriptase-PCR, Western blot analysis, and immunohistochemistry showed that seminal plasma FH is mainly secreted from epithelial cells of the seminal vesicle in male genital tracts. FH was also detected in the outer acrosomal region of ejaculated sperm by immunofluorescence staining, and found that the purified FH from the sperm membrane has the same complement regulatory activity as that of seminal plasma FH. The ejaculated sperm possessing FH in the outer acrosomal region considerably evaded complement attack. We also found that there is strong complement activity in fluids from female genital tract ducts. These findings indicate that FH bound to the outer acrosomal region and soluble FH play important roles in protecting sperm against complement attack in male and female genital tracts.

show abstract

Membrane cofactor protein (MCP, CD46) in seminal plasma and on spermatozoa in normal and “sterile” subjects

Cited by 52 publications

References 35 publications

Identification and characterization of a silencer regulatory element in the 3′-flanking region of the murine CD46 gene

Identification and characterization of a silencer regulatory element in the 3′-flanking region of the murine CD46 gene

Interaction of Glycoprotein H of Human Herpesvirus 6 with the Cellular Receptor CD46

Factor H in Porcine Seminal Plasma Protects Sperm against Complement Attack in Genital Tracts

Contact Info

Product

Resources

About