Revisiting the Role of H super(+) in Chemotactic Signaling of Sperm

Chemotaxis of sperm is an important step toward fertilization. During chemotaxis, sperm change their swimming behavior in a gradient of the chemoattractant that is released by the eggs, and finally sperm accumulate near the eggs. A well established model to study chemotaxis is the sea urchin Arbacia punctulata. Resact, the chemoattractant of Arbacia, is a peptide that binds to a receptor guanylyl cyclase. The signaling pathway underlying chemotaxis is still poorly understood. Stimulation of sperm with resact induces a variety of cellular events, including a rise in intracellular pH (pH sub(i)) and an influx of Ca super(2+); the Ca super(2+) entry is essential for the chemotactic behavior. Previous studies proposed that the influx of Ca super(2+) is initiated by the rise in pH sub(i). According to this proposal, a cGMP-induced hyperpolarization activates a voltage-dependent Na super(+)/H super(+) exchanger that expels H super(+) from the cell. Because some aspects of the proposed signaling pathway are inconsistent with recent results (Kaupp, U.B., J. Solzin, J.E. Brown, A. Helbig, V. Hagen, M. Beyermann, E. Hildebrand, and I. Weyand. 2003. Nat. Cell Biol. 5:109-117), we reexamined the role of protons in chemotaxis of sperm using kinetic measurements of the changes in pH sub(i) and intracellular Ca super(2+) concentration. We show that for physiological concentrations of resact (