Trp2 regulates entry of Ca²⁺ into mouse sperm triggered by egg ZP3

Abstract

In many cells, receptor activation initiates sustained Ca²⁺ entry which is critical in signal transduction¹. Mammalian transient receptor potential (Trp) proteins, which are homologous to the Drosophila photoreceptor-cell Trp protein, have emerged as candidate subunits of the ion channels that mediate this influx. As a consequence of overexpression, these proteins produce cation currents that open either after depletion of internal Ca²⁺ stores or through receptor activation². However, determining the role of endogenous Trp proteins in signal transduction is complicated by the absence of selective antagonists. Here we examine Trp function during sperm–egg interaction. The sperm acrosome reaction is a Ca²⁺-dependent secretory event that must be completed before fertilization. In mammals, exocytosis is triggered during gamete contact by ZP3, a glycoprotein constituent of the egg's extracellular matrix, or zona pellucida (ZP). ZP3 activates trimeric G proteins and phospholipase C and causes a transient Ca²⁺ influx into sperm through T-type Ca²⁺ channels³. These early responses promote a second Ca²⁺-entry pathway, thereby producing sustained increases in intracellular Ca²⁺ concentration ([Ca²⁺]_i) that drive acrosome reactions⁴. Our results show that Trp2 is essential for the activation of sustained Ca²⁺ influx into sperm by ZP3.