@article{667814534e95462f879f0a914b01c701,
title = "A male-derived nonribosomal peptide pheromone controls female schistosome development",
abstract = "Schistosomes cause morbidity and death throughout the developing world due to the massive numbers of eggs female worms deposit into the blood of their host. Studies dating back to the 1920s show that female schistosomes rely on constant physical contact with a male worm both to become and remain sexually mature; however, the molecular details governing this process remain elusive. Here, we uncover a nonribosomal peptide synthetase that is induced in male worms upon pairing with a female and find that it is essential for the ability of male worms to stimulate female development. We demonstrate that this enzyme generates β-alanyl-tryptamine that is released by paired male worms. Furthermore, synthetic β-alanyl-tryptamine can replace male worms to stimulate female sexual development and egg laying. These data reveal that peptide-based pheromone signaling controls female schistosome sexual maturation, suggesting avenues for therapeutic intervention and uncovering a role for nonribosomal peptides as metazoan signaling molecules.",
keywords = "nonribosomal peptide, NRPS, reproductive biology, schistosomes",
author = "Rui Chen and Jipeng Wang and Irina Gradinaru and Vu, {Hieu S.} and Sophie Geboers and Jacinth Naidoo and Ready, {Joseph M.} and Williams, {Noelle S.} and DeBerardinis, {Ralph J.} and Ross, {Elliott M.} and Collins, {James J.}",
note = "Funding Information: We thank members from Collins lab, Phillip A. Newmark, and Melanie H. Cobb for comments on the manuscript; the NIAID Schistosomiasis Resource Center of the Biomedical Research Institute (Rockville, MD) for providing infected snails and infected mice through NIH-NIAID contract HHSN272201700014I for distribution through BEI Resources; Helmut Kr{\"a}mer for providing Ebony cDNA; the UT Southwestern Electron Microscopy and Genomics Core Facilities; and Francisco Ortiz from Preclinical Pharmacology Core Lab. Biorender was used for some schematic material. This work was funded by NIH grants R01AI121037 (J.J.C.), R01AI150776 (J.J.C.), and R35CA22044901 (R.J.D.); Welch Foundation grant I-1948-20180324 (J.J.C.); and the Burroughs Wellcome Fund (J.J.C.). R.J.D. is an HHMI investigator. Funding Information: We thank members from Collins lab, Phillip A. Newmark, and Melanie H. Cobb for comments on the manuscript; the NIAID Schistosomiasis Resource Center of the Biomedical Research Institute (Rockville, MD) for providing infected snails and infected mice through NIH-NIAID contract HHSN272201700014I for distribution through BEI Resources; Helmut Kr{\"a}mer for providing Ebony cDNA; the UT Southwestern Electron Microscopy and Genomics Core Facilities; and Francisco Ortiz from Preclinical Pharmacology Core Lab. Biorender was used for some schematic material. This work was funded by NIH grants R01AI121037 (J.J.C.), R01AI150776 (J.J.C.), and R35CA22044901 (R.J.D.); Welch Foundation grant I-1948-20180324 (J.J.C.); and the Burroughs Wellcome Fund (J.J.C.). R.J.D. is an HHMI investigator. Conceptualization, R.C. J.W. and J.J.C.; methodology, R.C. J.W. E.M.R. and J.J.C.; formal analysis, J.J.C.; investigation, R.C. J.W. I.G. H.S.V. and S.G.; resources, J.N. and J.M.R.; writing – original draft, R.C. and J.J.C.; writing – review & editing, R.C. E.M.R. and J.J.C.; visualization, R.C. and J.J.C.; supervision, J.M.R. N.S.W. R.J.D. E.M.R. and J.J.C.; project administration, R.C. J.W. and J.J.C.; funding acquisition, J.J.C. and R.J.D. R.J.D. is on the SABs for Agios Pharmaceuticals, Vida Ventures, and Nirogyone Therapeutics and is a founder/advisor for Atavistik Biosciences. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = apr,
day = "28",
doi = "10.1016/j.cell.2022.03.017",
language = "English (US)",
volume = "185",
pages = "1506--1520.e17",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "9",
}