A network of interactions among seminal proteins underlies the long-term postmating response in Drosophila

Despite the importance of seminal proteins in fertility and their capacity to alter mated females' physiology, the molecular pathways and networks through which they act have not been well characterized. Drosophila seminal fluid includes proteins that fall into biochemical classes conserved from insects to mammals, making it an excellent model with which to address this question. Drosophila seminal fluid also contains a "sex peptide" (SP, Acp70A) that plays a major role in regulating egg production and mating behavior in females for several days after mating. This long-term postmating response (LTR) initially requires the association of SP with sperm. The LTR also requires members of the conserved seminal protein classes (two lectins, a protease, and a cysteine-rich secretory protein). Here, we show that these seminal proteins function interdependently, regulating a three-step cascade (first, at the level of seminal protein transfer to the female; second, at the level of stability; and third, at the level of localization within females), leading to the normal localization of SP to sperm-storage organs. This localization is, in turn, necessary for successful induction of the LTR. The requirements for manifestation of the LTR in Drosophila establish the paradigm that multiple seminal proteins can exert their actions through a multistep, multicomponent network of interactions.