A role for sperm surface protein disulfide isomerase activity in gamete fusion: evidence for the participation of ERp57.
In mammals, sperm-egg interaction is based on molecular events either unique to gametes or also present in somatic cells. In gamete fusion, it is unknown which features are gamete specific and which are shared with other systems. Conformational changes mediated by thiol-disulfide exchange are involved in the activation of some virus membrane fusion proteins. Here we asked whether that mechanism is also operative in sperm-egg fusion. Different inhibitors of protein disulfide isomerase (PDI) activity were able to inhibit sperm-egg fusion in vitro. While pretreatment of oocytes had no effect, pretreatment of sperm reduced their fusion ability. Some members of the PDI family were detected on the sperm head, and use of specific antibodies and substrates suggested that the oxidoreductase ERp57 has a role in gamete fusion. The results support the idea that thiol-disulfide exchange is a mechanism that may act in gamete fusion to produce conformational changes in fusion-active proteins.
Ellerman
Diego A
DA
Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, Davis, California 95616, USA. daellerman@ucdavis.edu
Myles
Diana G
DG
Primakoff
Paul
P
D020101:Acrosome Reaction; D000818:Animals; D001414:Bacitracin / Q000494:pharmacology; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D050576:Membrane Fusion Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D013084:Sperm-Ovum Interactions; D013094:Spermatozoa / Q000737:chemistry* / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D050576:Membrane Fusion Proteins; D013439:Sulfhydryl Reagents; D001414:Bacitracin; D004228:Dithionitrobenzoic Acid; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases