Receptors and channels regulating acrosome reactions

Abstract

Prospective clinical studies informed by cloning and sequencing of sperm surface receptors and metal ion channels have elucidated critical early steps in the acrosome reaction that explain aspects of metal ion-related male infertility. Induction of the acrosome reaction is proposed to include non-nuclear progesterone receptor activation of Shaker-related sperm head voltage-gated potassium ion channels (VGKC). Men express VGKC isoforms with differing sensitivities to lead (Pb²⁺) inhibition, thus explaining interindividual variabilities in Pb²⁺-related male infertility. VGKC opening induces calcium (Ca²⁺) transients, and a signalling cascade induced by zona receptor aggregation requires an actin cytoskeleton created by the VGKC-induced Ca²⁺ transients. Actin polymerization and stabilization, favoured by zinc (Zn²⁺) and depolymerized by cadmium (Cd²⁺), may mediate low Zn²⁺ and high Cd²⁺ infertile states. Zona receptor aggregation induces phosphotyrosine signals at sites, including sperm voltage-dependent Ca²⁺ channels (VDCC), intermediate in electrophysiology between T- and L-type channels. Sperm surface VDCC localize at the sperm equatorial segment, the terminus of zona receptor translocation. Opening of VDCC admits a second Ca²⁺ wave that activates phospholipase C phosphorylated in the zona receptor cascade. Phospholipase C induces fusogenic lipids and activates actin-severing proteins, deploymerizing the actin cytoskeleton and permitting apposition and fusion of acrosomal and plasma membranes.