Phosphoinositide-dependent pathways in mouse sperm are regulated by egg ZP3 and drive the acrosome reaction.
Sperm of many animals must complete an exocytotic event, the acrosome reaction, in order to fuse with eggs. In mammals, acrosome reactions are triggered during sperm contact with the egg extracellular matrix, or zona pellucida, by the matrix glycoprotein ZP3. Here, we show that ZP3 stimulates production of phosphatidylinositol-(3,4,5)-triphosphate in sperm membranes. Phosphatidylinositol-3-kinase antagonists that prevent acrosome reactions and fertilization in vitro, while generation of this phosphoinositide in the absence of ZP3 triggered acrosome reactions. Downstream effectors of phosphatidylinositol-(3,4,5)-triphosphate in sperm include the protein kinases, Akt and PKCzeta. These studies outline a signal transduction pathway that plays an essential role in the early events of mammalian fertilization.
Jungnickel
Melissa K
MK
Department of Cell Biology, University of Massachusetts, 55 Lake Avenue North, Worcester, MA 01655, USA.
Sutton
Keith A
KA
Wang
Yanli
Y
Florman
Harvey M
HM
D020101:Acrosome Reaction / Q000502:physiology*; D000818:Animals; D004527:Egg Proteins / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D008055:Lipids / Q000032:analysis; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology*; D000072216:Zona Pellucida Glycoproteins
D004527:Egg Proteins; D008055:Lipids; D008562:Membrane Glycoproteins; D018129:Phosphatidylinositol Phosphates; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse; C060974:phosphatidylinositol 3,4,5-triphosphate