RT Journal Article SR Electronic T1 BMP signaling inhibition in Drosophila secondary cells remodels the seminal proteome and self and rival ejaculate functions JF Proceedings of the National Academy of Sciences JO Proc Natl Acad Sci USA FD National Academy of Sciences SP 24719 OP 24728 DO 10.1073/pnas.1914491116 VO 116 IS 49 A1 Hopkins, Ben R. A1 Sepil, Irem A1 Bonham, Sarah A1 Miller, Thomas A1 Charles, Philip D. A1 Fischer, Roman A1 Kessler, Benedikt M. A1 Wilson, Clive A1 Wigby, Stuart YR 2019 UL http://www.pnas.org/content/116/49/24719.abstract AB How are ejaculates built? Fertility-enhancing seminal fluid is the product of many different glands and cells, but how the function and composition of seminal fluid emerges from these different elements is poorly resolved. Here, we characterize the contributions of the functionally cryptic Drosophila accessory gland secondary cells to ejaculate composition and reproductive outcome. We find that in adults these cells are central to the regulation of the seminal proteome, the promotion of normal sperm behavior, and the induction of many, but not all, postmating responses. Our results illustrate interdependency between glandular cell types, identify constraints in ejaculate functions linked to male reproductive success, and provide insights into the design and production of ejaculates.Seminal fluid proteins (SFPs) exert potent effects on male and female fitness. Rapidly evolving and molecularly diverse, they derive from multiple male secretory cells and tissues. In Drosophila melanogaster, most SFPs are produced in the accessory glands, which are composed of ∼1,000 fertility-enhancing “main cells” and ∼40 more functionally cryptic “secondary cells.” Inhibition of bone morphogenetic protein (BMP) signaling in secondary cells suppresses secretion, leading to a unique uncoupling of normal female postmating responses to the ejaculate: refractoriness stimulation is impaired, but offspring production is not. Secondary-cell secretions might therefore make highly specific contributions to the seminal proteome and ejaculate function; alternatively, they might regulate more global—but hitherto undiscovered—SFP functions and proteome composition. Here, we present data that support the latter model. We show that in addition to previously reported phenotypes, secondary-cell-specific BMP signaling inhibition compromises sperm storage and increases female sperm use efficiency. It also impacts second male sperm, tending to slow entry into storage and delay ejection. First male paternity is enhanced, which suggests a constraint on ejaculate evolution whereby high female refractoriness and sperm competitiveness are mutually exclusive. Using quantitative proteomics, we reveal changes to the seminal proteome that surprisingly encompass alterations to main-cell–derived proteins, indicating important cross-talk between classes of SFP-secreting cells. Our results demonstrate that ejaculate composition and function emerge from the integrated action of multiple secretory cell types, suggesting that modification to the cellular make-up of seminal-fluid-producing tissues is an important factor in ejaculate evolution.