The biochemistry of the acrosome reaction

The binding of the spermatozoon to the oocyte zona pellucida (ZP) occurs via specific receptors localized over the anterior head region of the spermatozoon. Zona pellucida binding stimulates the spermatozoa to undergo the acrosome reaction resulting in the release of hydrolytic enzymes and in the exposure of new membrane domains, both of which are essential for fertilization. We suggest that ZP binds to at least two different receptors in the plasma membrane. One (R) is a G_i-coupled receptor that activates phospholipase C (PLC)β₁. The other (TK) is a tyrosine kinase receptor coupled to PLCγ. Binding to R would regulate adenylyl cyclase (AC) leading to elevation of cAMP and protein kinase (PKA) activation. The PKA activates a voltage-dependent Ca²⁺ channel in the outer acrosomal membrane which releases Ca²⁺ from the interior of the acrosome to the cytosol. This is the first, relatively small, rise in [Ca²⁺]_i (I) which leads to activation of the PLCγ. The products of phosphatidyl-inositol bisphosphate (PIP₂) hydrolysis by PLC diacylglycerol (DAG) and inositol-trisphosphate (IP₃) will lead to PKC translocation to the plasma membrane and its activation. PKC opens a voltage-dependent Ca²⁺ channel (L) in the plasma membrane, leading to the second (II) higher increase in [Ca²⁺]_i. The G_i or TK can also activate an Na⁺/H⁺ exchanger leading to alkalization of the cytosol. PKC also activates phospholipase A₂ (PLA₂) to generate arachidonic acid (AA) from membrane phospholipids. AA will be converted to prostaglandins (PG) and leukotriens (LT) by the enzymes cyclooxygenase (COX) and lipoxygenase (LOX) respectively. The increase in [Ca²⁺]_i and pH leads to membrane fusion and acrosomal exocytosis.