title: Regulatory mechanisms in acrosomal exocytosis.
abstract: Acrosomal exocytosis occurs after the binding of the spermatozoon to the zona pellucida of the oocyte via specific receptors. We suggest that the zona pellucida binds to at least two different receptors in the plasma membrane. One (R) is a Gi-coupled receptor that activates phospholipase C beta 1. The other (TK) is a tyrosine kinase receptor coupled to phospholipase C gamma. Binding to R would regulate adenylyl cyclase leading to an increase in cyclic adenosine monophosphate and protein kinase A activation. The protein kinase A activates a voltage-dependent Ca2+ channel in the outer acrosomal membrane that releases Ca2+ from the interior of the acrosome to the cytosol. This is the first (I), relatively small, rise in intracellular Ca2+ which leads to activation of the phospholipase C gamma. The products of phosphatidyl-inositol bisphosphate hydrolysis by phospholipase C, diacylglycerol and inositol-trisphosphate lead to protein kinase C translocation to the plasma membrane and its activation. Protein kinase C opens a voltage-dependent Ca2+ channel (L) in the plasma membrane, leading to the second (II), higher, increase in intracellular Ca2+ leading to acrosomal exocytosis. Spermine, a physiological constituent of the seminal plasma regulates sperm acrosomal exocytosis by modulating intracellular Ca2+ binding sites and phospholipase C activity. Spermine is rapidly incorporated into the sperm cells during ejaculation and temporarily inhibits premature capacitation and acrosome reaction. During the passage of the spermatozoon through the female genital tract, there is a progressive depletion of spermine from spermatozoa, so that capacitation and consequently the acrosomal exocytosis take place at the appropriate time, when the spermatozoon reaches the vicinity of the egg.
authors.affiliation: Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Breitbart
authors.forename: S
authors.initials: S
authors.lastname: Rubinstein
authors.forename: Y
authors.initials: Y
authors.lastname: Lax
mesh_terms: D000177:Acrosome / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D015398:Signal Transduction / Q000502:physiology*; D013096:Spermine / Q000378:metabolism; D015044:Zona Pellucida / Q000502:physiology*
chemical_list: D013096:Spermine