title: Mechanism of sperm-zona pellucida penetration during mammalian fertilization: 26S proteasome as a candidate egg coat lysin.
abstract: Despite years of research work, biologists remain divided over the issue of zona pellucida function during fertilization and the mode of sperm-ZP penetration. The present review examines the emerging evidence for the participation of ubiquitin-proteasome pathway in the process of sperm-ZP penetration generated in the last five years in species of mammals, ascidians and invertebrates. The 26S proteasome, a multi-subunit protease, selectively recognizes, and degrades, egg coat substrate proteins tagged by a covalent ligation of a small, multimeric protein, ubiquitin. Our in vitro work with pig gametes indicates that the sperm-borne 26S proteasomes selectively degrade an ubiquitinated ZP (glyco)protein during fertilization. We suggest that one or more of the ZP proteins are ubiquitinated, and proteasomes associated with the inner acrosomal membrane, are exposed as a result of acrosomal exocytosis. Sperm-ZP penetration may involve the ZP-deubiquitination, with several proteasomal subunits becoming phosphorylated. Polyubiquitin chain recognition activities associated with the sperm acrosomal proteasome could also contribute to anti-polyspermy control after sperm-egg fusion. Here, we bring together the relevant recent data on the mechanism of sperm-ZP penetration in mammals. Such observations could possibly lead to the development of novel non-hormonal contraceptives, improvement of infertility diagnostics and optimization of assisted reproduction.
authors.affiliation: Division of Animal Sciences, Departments of Obstetrics & Gynecology, University of Missouri-Columbia, Columbia, MO 65211, USA.
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Yi
authors.forename: Gaurishankar
authors.initials: G
authors.lastname: Manandhar
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Oko
authors.forename: William G
authors.initials: WG
authors.lastname: Breed
authors.forename: Peter
authors.initials: P
authors.lastname: Sutovsky
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D008322:Mammals / Q000502:physiology*; D046529:Microscopy, Electron, Transmission; D023421:Models, Animal; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D013077:Sperm Head / Q000201:enzymology* / Q000648:ultrastructure; D013084:Sperm-Ovum Interactions / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism; D015044:Zona Pellucida / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease