Human seminal clusterin (SP-40,40). Isolation and characterization.

O'Bryan, Moira K; Baker, H. W. G.; Saunders, Jocelyn R.; Kirszbaum, L.; Walker, Ian D.; Hudson, Peter J.; Liu, D. Y.; Glew, Michelle D.; d’Apice, Anthony J.F.; Murphy, Brendan

doi:10.1172/jci114594

Cited by 122 publications

(66 citation statements)

References 19 publications

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“…Clusterin is also involved in the development of Alzheimer's disease (12). The presence of high concentrations of clusterin in seminal plasma (0.4-15.0 mg/ml) was reported previously (22)(23)(24), and a role in sperm development has also been proposed (24).…”

Section: Endritic Cells (Dcs) Are Highly Specialized Professionalmentioning

confidence: 61%

Semen Clusterin Is a Novel DC-SIGN Ligand

Sabatté

Faigle

Ceballos

et al. 2011

The Journal of Immunology

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The C-type lectin receptor dendritic cell-specific ICAM-3–grabbing nonintegrin (DC-SIGN) is an important player in the recognition of pathogens by dendritic cells. A plethora of pathogens including viruses, bacteria, parasites, and fungi are recognized by DC-SIGN through both mannose and fucose-containing glycans expressed on the pathogen surface. In this study, we identified semen clusterin as a novel DC-SIGN ligand. Semen clusterin, but not serum clusterin, expresses an extreme abundance of fucose-containing blood-type Ags such as Lex and Ley, which are both excellent DC-SIGN ligands. These motifs enable semen clusterin to bind DC-SIGN with very high affinity (Kd 76 nM) and abrogate the binding of HIV-1 to DC-SIGN. Depletion of clusterin from semen samples, however, did not completely prevent the ability of semen to inhibit the capture of HIV-1 by DC-SIGN, supporting that besides clusterin, semen contains other DC-SIGN ligands. Further studies are needed to characterize these ligands and define their contribution to the DC-SIGN–blocking activity mediated by semen. Clusterin is an enigmatic protein involved in a variety of physiologic and pathologic processes including inflammation, atherosclerosis, and cancer. Our results uncover an unexpected heterogeneity in the glycosylation pattern of clusterin and suggest that the expression of high concentrations of fucose-containing glycans enables semen clusterin to display a unique set of biological functions that might affect the early course of sexually transmitted infectious diseases.

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Section: Endritic Cells (Dcs) Are Highly Specialized Professionalmentioning

confidence: 61%

Semen Clusterin Is a Novel DC-SIGN Ligand

Sabatté

Faigle

Ceballos

et al. 2011

The Journal of Immunology

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“…Early studies of CLU gene products reported divergent 5 0 -untranslated regions (5 0 -UTR) in RNAs from rats (Collard & Griswold 1987, Wong et al 1993, humans (Jenne & Tschopp 1989, Kirszbaum et al 1989, O'Bryan et al 1990) and mice (French et al 1993, Jordan-Starck et al 1994. Therefore, the possibility of alternative first exons for CLU transcription products in different mammalian species was already known at that time.…”

Section: Clu Gene and Transcriptsmentioning

confidence: 99%

The clusterin paradigm in prostate and breast carcinogenesis

Rizzi¹,

Bettuzzi²

2010

Endocrine-Related Cancer

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The biological functions of clusterin (CLU, also known as ApoJ, SGP2, TRPM-2, CLI) have been puzzling the researchers since its first discovery in the early 80's. We know that CLU is a single 9-exons gene expressing three protein forms with different sub-cellular localisations and diverse biological functions. Despite the many reports from many research teams on CLU action and its relation to tumourigenesis, contradictions in the data and alternative hypothesis still exist. Understanding the role of CLU in tumourigenesis is complicated not only by the existence of different protein forms but also by the changes of tumours over time and the selection pressures imposed by treatments such as hormone ablation or chemotherapy. This review focuses on recent discoveries concerning the role of CLU in prostate and breast cancer onset and progression. Although CLU acts primarily as a tumour suppressor in the early stages of carcinogenesis, consistent with its role in the involution of the prostate following castration, late stage cancer may overexpress CLU following chemotherapeutic drugs or hormonal ablation therapy. High expression of secreted or cytoplasmic CLU may represent a pro-survival stimulus because it confers increased resistance to killing by anti-cancer drugs or enhances tumour cell survival in specific niches.

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“…It prevents oxidative damage to cells (Reyes-Moreno et al, 2002), agglutinates abnormal spermatozoa in bulls (Ibrahim et al, 1999) and acts like a chaperone, protecting sperm from the toxic effects of protein precipitation (Humphreys et al, 1999). Clusterin has the ability to inhibit complement-induced sperm lysis (Ibrahim et al, 1999;O'Bryan et al, 1990), another form to preserve sperm cell integrity.…”

Section: Proteome Of Seminal Fluidmentioning

confidence: 99%