THE BIOCHEMISTRY OF THE ACROSOME REACTION

The binding of the spermatozoon to the oocyte zona pellucida (ZP) occu rs via specific receptors localized over the anterior head region of t he spermatozoon. Zona pellucida binding stimulates the spermatozoa to undergo the acrosome reaction resulting in the release of hydrolytic e nzymes 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)beta(1). The other (TK) i s a tyrosine kinase receptor coupled to PLC gamma. Binding to R would regulate adenylyl cyclase (AC) leading to elevation of cAMP and protei n kinase (PKA) activation. The PKA activates a voltage-dependent Ca2channel in the outer acrosomal membrane which releases Ca2+ from the i nterior of the acrosome to the cytosol. This is the first, relatively small, rise in [Ca2+](i) (I) which leads to activation of the PLC gamm a. The products of phosphatidyl-inositol bisphosphate (PIP2) hydrolysi s by PLC diacylglycerol (DAG) and inositol-trisphosphate (IP3) will le ad to PKC translocation to the plasma membrane and its activation. PKC opens a voltage-dependent Ca2+ channel (L) in the plasma membrane, le ading 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 c ytosol. PKC also activates phospholipase A(2) (PLA(2)) to generate ara chidonic acid (AA) from membrane phospholipids. AA will be converted t o prostaglandins (PG) and leukotriens (LT) by the enzymes cyclooxygena se (COX) and lipoxygenase (LOX) respectively. The increase in [Ca2+](i ) and pH leads to membrane fusion and acrosomal exocytosis.