ZP3-dependent activation of sperm cation channels regulates acrosomal secretion during mammalian fertilization.
The sperm acrosome reaction is a Ca(2+)-dependent secretory event required for fertilization. Adhesion to the egg's zona pellucida promotes Ca2+ influx through voltage-sensitive channels, thereby initiating secretion. We used potentiometric fluorescent probes to determine the role of sperm membrane potential in regulating Ca2+ entry. ZP3, the glycoprotein agonist of the zona pellucida, depolarizes sperm membranes by activating a pertussis toxin-insensitive mechanism with the characteristics of a poorly selective cation channel. ZP3 also activates a pertussis toxin-sensitive pathway that produces a transient rise in internal pH. The concerted effects of depolarization and alkalinization open voltage-sensitive Ca2+ channels. These observations suggest that mammalian sperm utilize membrane potential-dependent signal transduction mechanisms and that a depolarization pathway is an upstream transducing element coupling adhesion to secretion during fertilization.
Arnoult
C
C
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Zeng
Y
Y
Florman
H M
HM
D000177:Acrosome / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002417:Cattle; D004527:Egg Proteins / Q000494:pharmacology*; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008564:Membrane Potentials; D051379:Mice; D037342:Pertussis Toxin; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000187:drug effects; D013084:Sperm-Ovum Interactions / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D015044:Zona Pellucida / Q000502:physiology*; D000072216:Zona Pellucida Glycoproteins
D015220:Calcium Channels; D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D010566:Virulence Factors, Bordetella; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse; D037342:Pertussis Toxin; D002118:Calcium