title: BMP-regulated exosomes from Drosophila male reproductive glands reprogram female behavior.
abstract: Male reproductive glands secrete signals into seminal fluid to facilitate reproductive success. In Drosophila melanogaster, these signals are generated by a variety of seminal peptides, many produced by the accessory glands (AGs). One epithelial cell type in the adult male AGs, the secondary cell (SC), grows selectively in response to bone morphogenetic protein (BMP) signaling. This signaling is involved in blocking the rapid remating of mated females, which contributes to the reproductive advantage of the first male to mate. In this paper, we show that SCs secrete exosomes, membrane-bound vesicles generated inside late endosomal multivesicular bodies (MVBs). After mating, exosomes fuse with sperm (as also seen in vitro for human prostate-derived exosomes and sperm) and interact with female reproductive tract epithelia. Exosome release was required to inhibit female remating behavior, suggesting that exosomes are downstream effectors of BMP signaling. Indeed, when BMP signaling was reduced in SCs, vesicles were still formed in MVBs but not secreted as exosomes. These results demonstrate a new function for the MVB-exosome pathway in the reproductive tract that appears to be conserved across evolution.
authors.affiliation: Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Corrigan
authors.affiliation: Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK.
authors.forename: Siamak
authors.initials: S
authors.lastname: Redhai
authors.affiliation: Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK.
authors.forename: Aaron
authors.initials: A
authors.lastname: Leiblich
authors.affiliation: Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK.
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Fan
authors.affiliation: Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK.
authors.forename: Sumeth M W
authors.initials: SM
authors.lastname: Perera
authors.affiliation: Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Patel
authors.affiliation: Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK.
authors.forename: Carina
authors.initials: C
authors.lastname: Gandy
authors.affiliation: Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK.
authors.forename: S Mark
authors.initials: SM
authors.lastname: Wainwright
authors.affiliation: Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK.
authors.forename: John F
authors.initials: JF
authors.lastname: Morris
authors.affiliation: Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK.
authors.forename: Freddie
authors.initials: F
authors.lastname: Hamdy
authors.affiliation: Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK.
authors.forename: Deborah C I
authors.initials: DC
authors.lastname: Goberdhan
authors.affiliation: Department of Physiology, Anatomy and Genetics and Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 3QX, England, UK clive.wilson@dpag.ox.ac.uk.
authors.forename: Clive
authors.initials: C
authors.lastname: Wilson
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster; D004847:Epithelial Cells / Q000378:metabolism; D055354:Exosomes / Q000502:physiology*; D005260:Female; D005836:Genitalia, Female / Q000166:cytology; D005837:Genitalia, Male / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008561:Membrane Fusion; D021962:Membrane Microdomains / Q000378:metabolism; D057146:Multivesicular Bodies / Q000378:metabolism; D021381:Protein Transport; D022142:Secretory Vesicles / Q000378:metabolism; D012726:Sexual Behavior, Animal; D015398:Signal Transduction; D013094:Spermatozoa / Q000378:metabolism; D060149:Tetraspanin 30 / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D060149:Tetraspanin 30