The sperm proteasome during sperm capacitation and fertilization

• Published in: Journal of reproductive immunology Vol. 83; no. 1; pp. 19 - 25
• Main Authors: Zimmerman, Shawn, Sutovsky, Peter
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Kidlington Elsevier Ireland Ltd 01.12.2009; Elsevier
• Subjects: Acrosome; Acrosome - physiology; Acrosome - ultrastructure; Animals; Biological and medical sciences; Embryology: invertebrates and vertebrates. Teratology; Fertilization; Fundamental and applied biological sciences. Psychology; Humans; Male; Models, Biological; Obstetrics and Gynecology; Proteasome; Proteasome Endopeptidase Complex - physiology; Sperm; Sperm Capacitation; Spermatozoa - physiology; Spermatozoa - ultrastructure; Ubiquitin; Ubiquitination; Zona pellucida; Ubiquitin; Fertilization; Acrosome; Sperm; Zona pellucida; Proteasome; Multicatalytic endopeptidase complex; Spermatozoa; Enzyme; Semen; Germinal cell; Fecundation; Peptidases; Reproduction; Vertebrata; Spermatozoid capacitation; Mammalia; Hydrolases; Oocyte
• ISSN: 0165-0378; 1872-7603
• DOI: 10.1016/j.jri.2009.07.006

Abstract The 26S proteasome is a multi-subunit protease specifically targeting ubiquitinated proteins. A consensus has emerged from studies by multiple laboratories on the role of sperm-borne proteasomes in human, mouse, pig, bovine, ascidian and echinoderm fertilization. Major findings from the studies in various mammalian and non-mammalian fertilization systems are (1) proteasomes are present in the mammalian sperm acrosome and on the acrosomal surface; (2) ubiquitinated proteins are present on the mammalian, ascidian and echinoderm egg coat; (3) proteasomal proteolytic and ubiquitin-deconjugating (deubiquitinating) activities can be detected in viable, motile mammalian spermatozoa; (4) proteasomes remain associated with the sperm head following ZP-induced acrosomal exocytosis; (5) inhibition of ubiquitination and proteasomal proteolysis blocks fertilization in mammals, ascidians and echinoderms; (6) inhibition of proteasomal proteolysis alters the course of mammalian sperm capacitation and acrosomal exocytosis induced by sperm binding to the egg coat, zona pellucida (ZP); (7) depletion of the sperm surface-associated ATP blocks porcine and echinoderm fertilization, most likely by affecting the integrity of sperm proteasomes, of which several subunits are ATPases; (8) inhibition of proteasomal proteolysis blocks sperm–ZP penetration, but does not alter the rate of sperm–ZP binding in mammals, and (9) experimental modification of sperm-associated deubiquitinating activities shifts the balance of monospermic fertilization to polyspermic fertilization in vitro . Altogether, these studies provide evidence for the involvement of the 26S proteasome in multiple steps of animal and human fertilization, offering a novel model of sperm–egg coat interactions, and identifying a range of potential new sperm quality markers and contraceptive targets.