First messengers at fertilization.

To investigate the 'first messengers' that pass between the spermatozoon and egg to initiate development, the function of G-proteins and membrane potential at fertilization have been examined. G-proteins are present in eggs, and activating them with GTP-gamma-S, cholera toxin, or receptors for serotonin or acetylcholine (expressed following mRNA injection) causes activation responses in eggs similar to those occurring at fertilization. ADP-ribosylation of most of the pertussis-sensitive G-proteins in Xenopus eggs does not block the responses to spermatozoa or serotonin. These results suggest that activation of a pertussis-insensitive G-protein may initiate activation responses in the egg at fertilization. In many species, one of these responses is a change in the egg's membrane potential, which prevents entry of additional spermatozoa. Results of cross-species fertilizations between voltage-sensitive and voltage-insensitive species indicate that the voltage-dependence of fertilization is due to the presence of a voltage-sensitive component in the sperm membrane, suggesting that the 'first messenger' is a positively charged component of the sperm membrane that inserts into the egg membrane to initiate sperm-egg fusion and egg activation.