Receptors and channels regulating acrosome reactions
Author: Benoff, Susan
Source: Human Fertility, Volume 2, Number 1, May 1999 , pp. 42-55(14)
Publisher: Informa Healthcare
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 (Pb 2+ ) inhibition, thus explaining interindividual variabilities in Pb 2+ -related male infertility. VGKC opening induces calcium (Ca 2+ ) transients, and a signalling cascade induced by zona receptor aggregation requires an actin cytoskeleton created by the VGKC-induced Ca 2+ transients. Actin polymerization and stabilization, favoured by zinc (Zn 2+ ) and depolymerized by cadmium (Cd 2+ ), may mediate low Zn 2+ and high Cd 2+ infertile states. Zona receptor aggregation induces phosphotyrosine signals at sites, including sperm voltage-dependent Ca 2+ 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 Ca 2+ 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.
Document Type: Research Article
Affiliations: Departments of Obstetrics and Gynecology and Cell Biology, New York University School of Medicine, New York, New York, USA
Publication date: 1999-05-01