Acrosomal exocytosis is initiated in mammalian sperm by stimulatory agonists in the zona pellucida. Recently, it was shown that exocytosis is modulated in bovine sperm by extrinsic factors present in seminal fluids (Florman, H.M., and First, N.L. (1988) Dev. Biol. 128, 464-474). Fractionation of bovine seminal fluids yields a M(r) approximately 6,500, basic (pI approximately 8.5) peptide that accounts for the positive modulation of zona pellucida-induced acrosome reaction (ED50 and maximal

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... nse at 0.2 and 1 micrograms/ml, respectively). In addition, application of purified peptide to fura 2-loaded, cauda epididymal sperm supported zona pellucida-promoted elevations of Ca2+i equivalent to those observed with sperm treated with unfractionated seminal fluids in vitro or in vivo. Finally, peptide treatment regulated gamete interaction in a manner consistent with the distinct behaviors of cauda epididymal and ejaculated bovine sperm. This purified seminal peptide was identified by sequence analysis as caltrin, a previously characterized regulator of Ca2+ transport in bovine sperm. We therefore propose that caltrin is a regulator of sperm signal transduction pathways activated by zona pellucida binding.