Model of phosphoinositide signaling during the ZP3-evoked acrosome reaction. PI(3,4,5)P3 levels are regulated by a constitutively active D3-phosphorylation/dephosphorylation cycle. ZP3 stimulation during sperm contact with the zona pellucida drives this cycle towards enhanced production of PI(3,4,5)P3. PI(3,4,5)P3 provides binding sites for PDK1 and facilitates it’s activation of the downstream targets, Akt and PKCζ. These downstream effectors are both required to drive sperm exocytosis.